diabetes type 2 clinical trials results

ACE inhibitor versus calcium-channel blocker
STOP-2 (ACEI vs CCB) (diabetic subgroup), 2000
ACE inhibitor
versus
calcium antagonists
diabetic (subgroup) elderly patients aged 70-84 years open with blind assessment
Follow-up duration: 5.03y
Sweden
ACE inhibitor versus diuretic or beta-blocker
STOP-2 (ACEI, diabetic subgroup), 2000
ACE inhibitor
versus
conventional treatment (diuretic or beta-blocker)
diabetic (subgroup) elderly patients aged 70-84 years with hypertensionopen with blind assessment
Follow-up duration: 5.03y
Sweden
ACE inhibitors versus placebo
HOPE (diabetic subgroup), 2000
ramipril 10 mg once per day orally
versus
placebo
patients with diabetes (sub group), aged 55 years or older, who had a previous cardiovascular event or at least one other cardiovascular risk factor, no clinical proteinuria, heart failure, or low ejection fractiondouble-blind
Follow-up duration: 4.5 years
North, South america, Europe
aggressive cholesterol-lowering versus moderate cholesterol-lowering
Post CABG (sub group), 1999
aggressive cholesterol-lowering
versus
moderate cholesterol-lowering
patients 1-11 years after CABGdouble blind
aggressive treatment versus standard teatment
SANDS, 2008
NCT00047424
aggressive targets of LDL-C of 70 mg/dL or lower and SBP of 115 mm Hg or lower
versus
standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower
adults with type 2 diabetes open
Follow-up duration: 3 years
US
AHA 2 diet versus AHA 1 diet
Liao, 2002
American Heart Association (AHA) step 2 diet (<30% of total calories as fat, <7% saturated fat, 55% carbohydrate, and < 200 mg cholesterol daily) plus endurance exercise for 1 h three times a week
versus
AHA step 1 diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and <300 mg cholesterol) plus stretching exercise three times a week
Japanese American subjects with impaired glucose tolerance (WHO criteria 1998)open
Follow-up duration: 22 months
USA
albiglutide versus placebo
Seino, 2009
NCT00530309
albiglutide 15 mg weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly
versus
placebo
Japanese subjects with type 2 diabetes mellitussingle-blind
Follow-up duration: 4 weeks (+5 wk)
Japan
albiglutide biweekly versus placebo (add on MET)
Rosenstock (30 mg every two weeks), 2009
NCT00518115
albiglutide 30mg weekly
versus
placebo
patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy double blind
Follow-up duration: 16 weeks
US, Mexico, Chile, Dominical republic
albiglutide weekly versus placebo (add on MET)
Rosenstock (30 mg weekly), 2009
NCT00518115
albiglutide 30mg weekly
versus
placebo
patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapydouble-blind
Follow-up duration: 16 weeks
US, Mexico, Chile, Dominical republic
aleglitazar versus placebo
ALECARDIO,
NCT01042769

versus
ALEPREVENT,
EUDRACT201200067116
aleglitazar 150 ìg
versus
placebo
patients with T2D or prediabetes with established, stable CV diseasedouble-blind
Follow-up duration: 58 days
ALECARDIO, 2014
NCT01042769
aleglitazar 150 ìg daily
versus
placebo
patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetesdouble-blind
Follow-up duration: 2 years ( median)
alogliptin versus placebo
EXAMINE, 2013
NCT00968708
alogliptin
versus
placebo
patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 daysdouble-blind
Follow-up duration: 1.5 years (median)
EXAMINE, 2011
NCT00968708

versus
alogliptin versus placebo (add on MET)
Nauck, 2009
NCT00286442
alogliptin 12.5 and 25 mg once daily
versus
placebo
patients whose HbA(1c) levels were inadequately controlled on metformin alonedouble-blind
Follow-up duration: 26 weeks
amlodipine versus atenolol
ASCOT (subgroup), 2008
amlodipine with addition of perindopril as required
versus
atenolol with addition of thiazide as required
Patients with untreated hypertension or treated hypertension; diabetic subgroup with two additionnal risk factorsdouble-blind
Follow-up duration: 5.7y
amlodipine versus chlorthalidone
ALLHAT (amlodipine vs chlor, diabetic subgroup), 2002
amlodipine
versus
chlorthalidone
diabetic (subgroup) participants aged 55 years or older with hypertensiondouble-blind
Follow-up duration: 4.9 y
amlodipine versus fosinopril
FACET, 1997
amlodipine (long acting) 10 mg daily
versus
fosinopril 20 mg daily
hypertensive patients with NIDDMopen
Follow-up duration: 3.5 y
Italy
amlodipine versus placebo
IDNT (amlodipine vs PBO), 2001
Amlodipine 10 mg daily
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetesdouble-blind
Follow-up duration: 2.6 years
Worldwide
aspart versus premix
Bretzel, 2004
preprandial insulin aspart
versus
human premix (70% NPH/30% regular) insulin
aspart + basal versus continuous infusion
Raskin, 2003
multiple daily injection bolus insulin aspart and basal NPH insulin
versus
continuous subcutaneous insulin infusion
aspert premix versus glargine + SU
Tamemoto, 2007
twice-daily 70/30 aspart premix
versus
once-daily glargine plus sulfonylurea
insulin-naive Japanese patients with type 2 diabetes patients insufficiently controlled with sulfonylurea open-label
aspirin versus no treatment
PPP (diabetics sub group), 2003
aspirin 100mg daily
versus
control
men and women with diabetes and without a previous cardiovascular event aged >50 with >=1 risk factors for cardiovascular disease - sub group of diabetic patientsopen
Follow-up duration: 3.6 y
Italy
JPAD, 2008
NCT00110448
low-dose aspirin (81 or 100 mg per day)
versus
no aspirin
patients with type 2 diabetes without a history of atherosclerotic diseaseopen
Follow-up duration: 4.37 y median
Japan
aspirin versus placebo
PHS (diabetics sub group), 1989
aspirin 325 mg every other day
versus
placebo
healthy men (diabetic sub group of patients enrolled if PHS)double blind
Follow-up duration: 5 y
ETDRS, 1992
aspirin 650mg once daily
versus
placebo
patients with diabetes mellitus (Type I or II)double blind
Follow-up duration: 60 months
WHS (diabetics sub group), 2005
aspirin 100mg on alternate days
versus
placebo
healthy women 45 years of age or older - diabetics sub groupsdouble blind
Follow-up duration: 10.1 y
US
POPADAD aspirin, 2008
ISRCTN53295293
aspirin 100mg daily
versus
placebo
patients with diabetes mellitus and asymptomatic peripheral arterial diseasedouble blind
Follow-up duration: nov 1997 - jul 2001
Scotland
DAMAD, 1989
aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily)
versus
placebo
patients with early diabetic retinopathydouble blind
Follow-up duration: 3 y
atorvastatin versus placebo
ASCOT (diabetics sub group), 2003
10 mg atorvastatin
versus
placebo
hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors
ASPEN, 2006
atorvastatin 10mg daily
versus
placebo
patients s with type 2 diabetes and LDL cholesterol levels below contemporary guideline targetsdouble blind
Follow-up duration: 4y
CARDS, 2004
NCT00327418
atorvastatin 10mg/d
versus
placebo
patients with type 2 diabetes without high concentrations of LDL-cholesterol and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension.double blind
Follow-up duration: 3.9 years
UK, Irelande
atorvastatin high dose versus atorvastatin
TNT (sub group), 2006
atorvastatin 80 mg daily
versus
atorvastatin 10 mg daily
patients with stable coronary heart disease double blind
Follow-up duration: 4.9 y
basal-bolus versus premix
GINGER (Fritsche), 2010
basal-bolus regimen with glargine and glulisine
versus
twice-daily premix
basal-bolus therapy versus biphasic insulin aspart 30
Liebl, 2009
analogue basal-bolus therapy (insulin detemir once daily and insulin aspart mealtimes)
versus
biphasic insulin aspart 30 twice daily
benazepril + amlodipine versus benazepril + hydrochlorothiazide
ACCOMPLISH (diabetic subgroup), 2010
NCT00170950
benazepril, combined with amlodipine
versus
benazepril, combined with hydrochlorothiazide
patients with diabetes (subgroup) and hypertension at high risk of cardiovascular and related eventsdouble-blind
Follow-up duration: 36 months
US, Norway, Denmark, Finland
BIAsp 30 + MET versus glargine + GLIM
Kann, 2006
twice-daily biphasic insulin aspart 30 + MET
versus
once-daily insulin glargine (glarg) plus glimepiride
insulin-naïve patients open-label
BIAsp 30)twice-daily + metformin versus once-daily glargine + metformin + secretagogues
Ligthelm, 2011
biphasic insulin aspart 70/30 (BIAsp 30)twice-daily + metformin
versus
once-daily glargine + metformin + secretagogues
type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugsopen-label
Follow-up duration: 24 weeks
BiAsp 70/30 versus NPH
Kilo, 2003
once-daily biphasic insulin aspart 70/30 (10 min before dinner)
versus
once daily NPH insulin (at 10 pm)
BIAsp 70/30 twice daily versus detemir once daily
4T (Holman), 2007
ISRCTN51125379
biphasic insulin aspart (NovoMix 30) twice daily
versus
basal insulin detemir once daily (twice if required)
patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea
Follow-up duration: 1 year
BIAsp 70/30 twice daily versus glargine once daily
Kalra, 2010
BIAsp 30 once-daily biphasic insulin aspart 70/30 (NovoMix 30 FlexPen)
versus
insulin glargine once daily
Asian subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs open-label
Follow-up duration: 26 weeks
Asia
INITIATE (Raskin), 2005
BIAsp 70/30, prebreakfast and presupper
versus
once-daily insulin glargine
insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADsopen-label
Follow-up duration: 28 weeks
Strojek, 2009
biphasic insulin aspart 30 (BIAsp 30) once daily
versus
insulin glargine once daily
patients with type 2 diabetes inadequately controlled with oral drugsopen-label
Follow-up duration: 26 weeks
BIAsp 70/30 twice daily versus NPH twice daily
Christiansen, 2003
Twice daily biphasic insulin aspart (BIAsp30)
versus
NPH insulin twice daily
patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents, NPH insulin or a combination of bothdouble-blind
Follow-up duration: 18 weeks
BID BIAsp 30 versus TID BIAsp 30
Yang, 2009
Thrice-daily biphasic insulin aspart 30
versus
BID BIAsp 30
Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents
China
biphasic aspert 30 versus multiple daily injections of insulin aspart
JDDM 11 (Hirao), 2008
twice-daily injections of biphasic insulin aspart 30
versus
multiple daily injections of insulin aspart
Japanese type 2 diabetic patients
biphasic insulin aspart 30 versus insulin detemir
Lundby, 2009
biphasic insulin aspart 30
versus
insulin detemir before bedtime
calcium-channel blocker versus diuretic or beta-blocker
STOP-2 (CCB, diabetic subgroup), 2000
Calcium-channel blocker
versus
diuretic or beta-blocker
diabetic (subgroup) elderly patients aged 70-84 years open with blind assessment
Follow-up duration: 5.03y
Sweden
canagliflozin versus placebo
CANVAS, 2017
NCT01032629

versus
candesartan versus control
SCOPE (diabetic subgroup), 2003
candesartan
versus
control
sub group of diabetic patients aged 70-89 years, with systolic blood pressure 160-179 mmHg, and/or diastolic blood pressure 90-99 mmHg, and a Mini Mental State Examination (MMSE) test score >or= 24double-blind
Follow-up duration: 3.7 years
15 countries
captopril versus atenolol
UKPDS 39, 1998
captopril 25 mg/d aiming at a BP <150/85
versus
atenolol 50mg/d aiming at a BP <150/85
hypertensive patients with type 2 diabetesopen
Follow-up duration: ND
UK
captopril versus diuretic and/or beta-blockers
CAPP (diabetic subgroup), 1999
Captopril initial dose of 50 mg daily given in one or two doses
versus
thiazide diuretic or beta-blocker
Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions; subgroup of diabetic patientsopen with blinded assessment
Follow-up duration: 6.1 year
Sweden, Finland
captopril or atenolol versus control
UKPDS 38, 1998
tight control of blood pressure aiming at a BP <150/85 (with the use of captopril or atenolol as main treatment, other treatment were added if the control criteria were not met)
versus
less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers)
hypertensive patients with type 2 diabetes open
Follow-up duration: 8.4y (median)
UK
carvedilol versus metoprolol
GEMINI, 2004
6.25- to 25-mg dose of carvedilol twice daily
versus
50- to 200-mg dose of metoprolol tartrate twice daily
patients with hypertension and type 2 diabetes mellitus receiving renin-angiotensin system blockadedouble-blind
Follow-up duration: 5 months
chlorthalidone versus placebo
SHEP (diabetic subgroup), 1996
low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed
versus
placebo
men and women aged 60 years and older , non-insulin-treated diabetic (sub group) patients with isolated systolic hypertension (systolic BP >= 160 mm Hg; diastolic BP, <90 mm Hg)double-blind
Follow-up duration: 5 year
combination versus placebo
POPADAD (antioxydant), 2008
ISRCTN53295293
antioxidant capsule containing (alpha-tocopherol 200 mg, ascorbic acid 100 mg, pyridoxine hydrochloride 25 mg, zinc sulphate 10 mg, nicotinamide 10 mg, lecithin 9.4 mg, and sodium selenite 0.8 mg)
versus
placebo
patients with diabetes mellitus and asymptomatic peripheral arterial diseasedouble blind
Scotland
dapagliflozin versus dlipizide add on metformin
Nauck, 2011
NCT00660907
Dapagliflozin in Combination With Metformin
versus
Sulphonylurea in Combination With Metformin
Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone
dapagliflozin versus placebo
Kohan,
NCT00972244
Dapagliflozin as Monotherapy
versus
placebo
Japanese Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
Kaku, 2014
NCT01294423

versus

Follow-up duration: 24 w
Japan
Ferrannini (MB102013), 2010
NCT00528372
a morning dose of 5 or 10 mg/day dapagliflozin
versus
placebo
treatment-naive patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
Komoroski (MB102007), 2009
NCT00162305
daily oral doses of 5-, 25-, or 100-mg doses of dapagliflozin
versus
placebo
patients with type 2 diabetes mellitus
Follow-up duration: 14 days
List (MB102008), 2009
NCT00263276
one of five dapagliflozin doses
versus
placebo
type 2 diabetic patients
Follow-up duration: 12 weeks
Kohan, 0
NCT00663260
Dapagliflozin
versus
placebo
Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment Who Have Inadequate Glycemic Contro
KOhan, 0
NCT00736879
Dapagliflozin monotherapy
versus
placebo
dapagliflozin versus placebo (add on insulin)
Wilding, 2012
NCT00673231
Dapagliflozin
versus
placebo on top of insulin
Type 2 Diabetes With Inadequate Glycaemic Control on Insulin
Wilding (MB102009), 2009
NCT00357370
10 mg dapagliflozin, or 20 mg dapagliflozin, plus OAD(s) and 50% of their daily insulin dose
versus
placebo
patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agentsdouble-blind
Follow-up duration: 12 weeks
US, Canada
dapagliflozin versus placebo (add on MET + SAXA)
Mathieu, 2015
NCT01646320

versus

Follow-up duration: 24 w
USA
dapagliflozin versus placebo (add on MET)
Bailey (MB102014), 2010
NCT00528879
dapagliflozin (2¡¤5 mg, n=137; 5 mg, n=137; or 10 mg, n=135)
versus
placebo
adults with type 2 diabetes who were receiving daily metformin (¡Ý1500 mg per day) and had inadequate glycaemic control double-blind
Follow-up duration: 24 weeks
Bolinder, 2012
NCT00855166
dapagliflozin
versus
placebo or Sitagliptin (on top MET)
Schumm-Draeger , 2015
NCT01217892
Dapagliflozin 2.5 mg BID, 5 mg BID and 10 mg QD
versus
placebo
Patients With Type 2 Diabetes Who Are Inadequately Controlled on Metformin-IR Monotherapy
dapagliflozin versus placebo (add on MET+SU)
Matthaei, 2015
NCT01392677

versus

Canada
dapagliflozin versus placebo (add on TZD)
Rosenstock, 2012
NCT00683878
Dapagliflozin in Combination With Thiazolidinedione
versus
Thiazolidinedione
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone
dapagliflozin versus placebo (on top standard treatment)
Leiter, 2016
NCT01042977
Dapagliflozin 10 mg tablet, oral, once daily, 24- week treatment
versus
placebo
Patients With T2DM and Cardiovascular Disease, Who Exhibit Inadequate Glycaemic Control on Usual Care
MB102035,
NCT00976495
Dapagliflozin Tablets, Oral, 10 mg, once daily, 12 weeks
versus
placebo
Cefalu, 2015
NCT01031680
Dapagliflozin 10 mg tablet, oral, once daily, 24- week
versus
placebo
MB102073,
NCT01137474
Dapagliflozin Tablets, Oral, 10 mg, once daily, up to 12 weeks
versus
placebo
patients with type 2 diabetes with uncontrolled hypertension who are on an Angiotensin-converting enzyme (ACE) inhibitor or an Angiotensin Receptor Blocker (ARB).
Weber,
NCT01195662
Dapagliflozin Tablets, Oral, 10 mg, once daily, Up to 12 weeks
versus
placebo
Subjects With Type 2 Diabetes With Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme (ACE) Inhibitor or Angiotensin Receptor Blocker (ARB) and an Additional Antihypertensive Medication
dapagliflozin versus placebo add on DPP-4
MB102061,
NCT00984867
Dapagliflozin 10 mg tablet, oral, once daily, 48 weeks
versus
placebo
Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on a DPP-4 Inhibitor Sitagliptin+/-Metformin
dapagliflozin versus Saxagliptin (add on MET)
Rosenstock, 2015
NCT01606007

versus

Follow-up duration: 24 w
USA
dapagliflozin + Glimepiride versus glimepiride
Strojek, 2011
NCT00680745
Dapagliflozin in Comb.With Glimepiride
versus
glimepiride alone
Type2 Diab.Who Have Inadeq. Glycaemic Control on Glimepiride Therapy Alone
dapagliflozin + merformin versus dapagliflozin
Kohan, 0
NCT00643851
Dapagliflozin in Combination With Metformin
versus
Dapagliflozin Monotherapy
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
dapagliflozin + merformin versus metformin or dapa
MB102034, 2016
NCT00859898
Dapagliflozin 10 mg in Combination With Metformin
versus
Dapagliflozin 10 mg Monotherapy or Metformin Monotherapy
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
detemir versus NPH insulin (add on aspart)
Haak ,
insulin detemir either once or twice daily according to their pretrial insulin treatment
versus
NPH insulin
patients with type 2 diabetesopen
Follow-up duration: 26 weeks
diltiazem versus diuretic and/or beta-blocker
NORDIL (diabetic subgroup), 2000
Diltiazem 180–360 mg diltiazem daily at step one
versus
thiazide diuretic or a beta-blocker at step one
diabetic patients (subgroup), aged 50-74 years who had diastolic blood pressure of 100 mm Hg or moreopen
Follow-up duration: 4.5 y
Norway, Sweden
empagliflozin versus Glimepiride + MET
Ridderstrale, 2014
NCT01167881
BI 10773 dose plus metformin
versus
Glimepiride 1-4 mg plus metformin

Follow-up duration: 104 w
USA
empagliflozin versus linagliptin (add-on MET)
DeFronzo, 2015
NCT01422876

versus
add-on to metformin for 52 weeks
subjects with type 2 diabetes inadequately controlled on metformin
empagliflozin versus linagliptin (monotherapy)
Lewin, 2015
NCT01422876
empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 135), empagliflozin 10 mg (n = 134)
versus
linagliptin 5 mg (n = 135) for 52 weeks
empagliflozin versus placebo
EMPA-REG OUTCOME, 0
NCT01131676

versus
Ferrannini, 2013
NCT00789035
empagliflozin 5, 10 or 25 mg once daily
versus
placebo
EMPA-REG MONO (Roden) vs placebo, 2013
NCT01177813

versus
Kadowaki, 2015
NCT01193218
empagliflozin (5, 10, 25, or 50 mg)
versus
placebo
Japanese patients with type 2 diabetes
EMPA-REG OUTCOME, 2015
NCT01131676
10 mg or 25 mg of empagliflozin once daily
versus
placebo
patients with type 2 diabetes at high cardiovascular riskdouble-blind
Follow-up duration: 3.1 years (median)
42 countries
Barnett, 2014
NCT01164501
/ BI 10773 low dose (BI 10773 tablets once daily) 2/ BI 10773 high dose (BI 10773 tablets once daily)
versus
Placebo
Patients With Mild or Moderate Renal Impairment
empagliflozin versus placebo (add on MET+/-PIO)
EMPA-REG PIO (Kovacs), 2013
NCT01210001
once daily empagliflozin 10 mg (n = 165), empagliflozin 25 mg
versus
add-on to pioglitazone ± metformin
empagliflozin versus placebo (add-on INS)
Rosenstock DOUBLON ???, 2013

versus
empagliflozin versus placebo (add-on INS+/-MET)
Rosenstock (1245.49), 2014
NCT01306214
once-daily empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189),
versus
placebo
Patients inadequately controlled on MDI insulin ± metformin
Follow-up duration: 18 weeks
USA
empagliflozin versus placebo (add-on MET)
Rosenstock, 2013
NCT00749190

versus
???
Ross, 2015
e2012-000905-53
empagliflozin 12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220),
versus
placebo
patients with type 2 diabetes inadequately controlled on metformin
EMPA-REG MET (Haring), 2014
NCT01159600
empagliflozin 10 mg (n = 217), empagliflozin 25 mg (n = 213),
versus
placebo
Patients with HbA1c levels of ¡Ý7% to ¡Ü 10% (¡Ý53 to ¡Ü86 mmol/mol) while receiving metformin (¡Ý1,500 mg/day)
empagliflozin versus placebo (add-on standard treatment)
Araki, 2015
NCT01368081
BI 10773 low dose (BI 10773 low dose tablet once daily) 2/ BI 10773 high dose (BI 10773 high dose tablet once daily)
versus
Metformin (Metformin tablets 500-2250 mg a day (twice or three times per day))
Japanese patients with type 2 diabetes mellitus
Follow-up duration: 52 w
Japan
enalapril versus placebo
SCAT (diabetic subgroup), 2000
enalapril 2.5mg twice daily
versus
placebo
normocholesterolemic patientsdouble-blind
Follow-up duration: Jun 1991 - Jul 1995
Canada
SOLVD (subgroup), 1996
enalapril
versus
placebo
patients with chronic heart failuredouble-blind
Follow-up duration: 3.5y
error versus placebo
Pan, 2003
acarbose 50 mg three times daily
versus
placebo
patients with impaired glucose tolerance (American Diabetes Association 1997 criteria)double blind
Follow-up duration: 16 weeks
China
STOP-NIDDM (Chiasson), 2002
acarbose 100mg three times daily
versus
placebo
patients with impaired glucose tolerance (WHO 1985 criteria)double blind
Follow-up duration: 3.3 years
Canada, Germany, Austria, Nordic countries, Spain, Israel
error versus placebo (add on to met)
Halimi, 2000
acarbose titrated up to 100 mg three times daily
versus
placebo
patients with Type 2 diabetes and inadequately controlled with metformin monotherapydouble-blind
Follow-up duration: 26 weeks
Rosenstock, 1998
acarbose forced titration from 25-50 mg t.i.d. and a titration of 50-100 mg tid that was based on glucose control
versus
placebo
patients with type 2 diabetes inadequately controlled with diet and metformin (2,000 or 2,500 mg/day in divided dosesdouble-blind
Follow-up duration: 24 weeks
exenatide versus glargine
NCT00360334,
NCT00360334

versus
exenatide versus placebo
Liutkus, 2010
exenatide twice-daily
versus
placebo
subjects suboptimally controlled with TZDs with or without metformin
exenatide 10µg twice daily versus liraglutide 1.8mg
LEAD 6 (Buse) exe vs lira, 2009

versus
exenatide 10µg/d versus placebo
H8O-MC-GWBJ, 9698, 10µg/d, 2008
exenatide twice daily 5 et 10 µg for 24 weeks
versus
placebo
Drug-Naive Patients with Type 2 Diabetes and inadequate glycemic control through diet and exercise double-blind
Follow-up duration: 24 weeks
4 countries
exenatide 10µg/d versus placebo (add on MET)
DeFronzo 10µg/d, 2005
NCT00039013
Exenatide 10–20 µg daily
versus
Placebo on-top of Metformin
patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin dosesdouble blind
Follow-up duration: 30 weeks
USA
exenatide 10µg/d versus placebo (add on SU)
Buse 10µg/d, 2004
NCT00039026
Exenatide 5µg twice daily
versus
Placebo on-top of SU
patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapydouble blind (not adequate)
Follow-up duration: 30 weeks
US
exenatide 10µg/d versus placebo (add on SU+/-MET/TZD)
Kadowaki (trial 8683), 2009
Exenatide 10µg daily for 12 weeks
versus
Placebo on-top of sulphonylureas +/-metformin/thiazolidinediones
Japanese patients with type 2 diabetes suboptimally controlled despite therapeutic dose of sulfonylurea, SU+biguanide or SU+thiazolidinedioneopen
Follow-up duration: 12 weeks
Japan
exenatide 10µg/d versus placebo (add on SU+MET)
Kendall 10µg/d, 2005
NCT00035984
Exenatide 5 µg bid
versus
Placebo on-top of sulphonylureas+metformin
patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy double blind
Follow-up duration: 30 weeks
USA
exenatide 10µg/d versus placebo add on MET+/-TZD
Gill, 2010
exenatide (5 microg for 4 weeks followed by 10 microg) for 12 weeks
versus
placebo
subjects with type 2 diabetes mellitus on metformin and/or a thiazolidinedionedouble-blind
Follow-up duration: 12 weeks
exenatide 20µg versus glibenclamide
Derosa, 2010
exenatide 10 microg twice a day
versus
glibenclamide 5 mg three times a day
patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin
exenatide 20µg/d versus BIAsp 30 daily
Bergenstal (once daily), 2009
exenatide(5 microg BID for 4 weeks and 10 microg BID thereafter)
versus
biphasic insulin aspart 70/30 (BIAsp 30) 30 QD (12 U before supper)
subjects with type 2 diabetes mellitus insulin naive, not achieving glycemic targets with metformin and sulfonylureaopen
Follow-up duration: 24 weeks
exenatide 20µg/d versus BIAsp 30 twice daily
Bergenstal (twice daily), 2009
exenatide (5 microg BID for 4 weeks and 10 microg BID thereafter)
versus
biphasic insulin aspart 70/30 (BIAsp 30) 30 BID (12 U divided equally between pre-breakfast and pre-supper)
subjects with type 2 diabetes mellitus insulin naive, not achieving glycemic targets with metformin and sulfonylurea open
exenatide 20µg/d versus insulin (add on SU+MET)
Heine, 2005
Exenatide 20 µg daily
versus
Insulin on-top of sulphonylureas+metformin
open
Follow-up duration: 26 weeks
exenatide 20µg/d versus insulin (add on SU/MET)
Barnett, 2007
NCT00099619
Exenatide 20 µg daily
versus
Insulin
patients with type 2 diabetesopen
Follow-up duration: 16 weeks
Australia, Greece,Hungary, Italy, Mexico, and Poland
Davis, 2007
NCT00099333
Exenatide 20 µg daily
versus
Insulin on-top of sulphonylureas/metformin
patients with type 2 diabetes using insulin in combination with oral antidiabetes agentsopen
Follow-up duration: 16 weeks
USA
exenatide 20µg/d versus insulin BIAsp twice daily add on SU+MET
Nauck, 2007
NCT00082407
Exenatide 20 µg daily
versus
Insulin on-top of sulphonylureas+metformin
patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metforminopen
Follow-up duration: 52 weeks
13 countries
exenatide 20µg/d versus insulin glargine (add on MET)
Bunck, 2009
NCT00097500
exenatide 10µg bid
versus
insulin glargine
metformin-treated patients with type 2 diabetes
Follow-up duration: 52 weeks
exenatide 20µg/d versus placebo
Apovian, 2010
10 microg exenatide twice daily injection + lifestyle modification program
versus
placebo + lifestyle modification program
overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylureadouble-blind
Follow-up duration: 24 weeks
H8O-MC-GWBJ, 9698, 20µg/d, 2008
exenatide twice daily 10 µg for 24 weeks
versus
placebo
Drug-Naive Patients with Type 2 Diabetes and inadequate glycemic control through diet and exercisedouble-blind
Follow-up duration: 24 weeks
4 countries
exenatide 20µg/d versus placebo (add on insulin)
Buse, 2011
NCT00765817
twice-daily 10 µg exenatide injections
versus
placebo (on top insulin glargine)
Adults with type 2 diabetes and an HbA1c level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents)double-blind
Follow-up duration: 30 weeks
Greece, Israel, Mexico, United Kingdom, USA
exenatide 20µg/d versus placebo (add on MET)
DeFronzo 20µg/d, 2005
NCT00039013
Exenatide 10–20 µg daily
versus
Placebo on-top of Metformin
patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses double blind
Follow-up duration: 30 weeks
USA
exenatide 20µg/d versus placebo (add on MET+/-SU)
Gao, 2009
NCT00324363
exenatide 5 mg then 10 mg twice-daily for 4 and 12 weeks
versus
placebo
Asian desccent with type 2 diabetes and inadequate glycemic control taking metformin alone or Met and sulfonylureas double-blind
Follow-up duration: 16 weeks
4 countries
exenatide 20µg/d versus placebo (add on SU)
Buse 20µg/d, 2004
Exenatide 10µg twice daily
versus
Placebo on-top of SU
patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy double blind (not adequate)
Follow-up duration: 30 weeks
US
exenatide 20µg/d versus placebo (add on SU+MET)
Kendall 20µg/d, 2005
NCT00035984
Exenatide 10 µg bid
versus
Placebo on-top of sulphonylureas+metformin
patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapydouble blind
Follow-up duration: 30 weeks
USA
exenatide 20µg/d versus placebo (add on TZD+/-MET)
Zinman 20µg/j, 2007
NCT00099320
Exenatide 20 µg daily
versus
Placebo on-top of thiazolidinediones+/-metformin
patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin) double blind
Follow-up duration: 16 weeks
Canada, Spain, and the United States
Zinman 20µg/j A MODIFIER, 2007
exenatide Subcutaneous abdominal injections of 10 microg twice daily
versus
placebo
patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin)double-blind
Follow-up duration: 16 weeks
Canada, Spain, and the United States
exenatide 20µg/d versus rosiglitazone add on MET
DeFronzo (EXE vs ROSI), 2010
EXE 10 microg b.i.d.
versus
ROSI 4 mg b.i.d.
subjects with type 2 diabetes on metforminopen
Follow-up duration: 20 weeks
exenatide 20µg/d versus sitagliptin (add on MET)
DeFronzo, 2008
NCT00477581
exenatide subcutaneous injection
versus
sitagliptin (100 mg QAM) for 2 weeks
metformin-treated T2D patientsdouble-blind
Follow-up duration: 2 weeks
USA
exenatide 20µg/d versus weekly exenatide
Drucker, 2008
NCT00308139
10 mug exenatide administered twice a day
versus
long-acting release formulation of exenatide 2 mg administered once weekly
patients with type 2 diabetes naive to drug therapy, or on one or more oral antidiabetic agentsopen
Follow-up duration: 30 weeks
exenatide before lunch and dinner versus exenatide before breakfast and dinner
Exenatide Trial 10749,
exenatide (10 ìg twice daily) administered subcutaneously before lunch and dinner
versus
exenatide (10 ìg twice daily) administered subcutaneously before breakfast and dinner
patients with type 2 Diabetes using oral antidiabetic therapyopen
2 countries
exenatide once monthly versus weekly exenatide
phase 2 exenatide once monthly,
exenatide once monthly at a low, medium or high dose, each administered once every four weeks, for a total of 20 weeks
versus
exenatide 2mg once weekly
adults with type 2 diabetes who were not achieving adequate glucose control using diet and exercise alone or with a stable regimen of metformin, pioglitazone, or bothopen
Follow-up duration: 20 weeks
exenatide other doses versus glargine
HEELA (Davies), 2009
exenatide 5¨C10 ¦Ìg bid
versus
insulin glargine o.d. (titrated to target fasting plasma glucose ¡Ü5.6 mmol/l)
Patients (BMI>27 kg/m2) with elevated cardiovascular risk and type 2 diabetes inadequately controlled on two or three oral antidiabetes drugs
exenatide other doses versus insulin glargine (add on MET/SU)
Trial 8078,
exenatide
versus
Insulin Glargine
Patients with Type 2 Diabetes Using Metformin or Sulfonylurea for Whom Insulin Is the Next Appropriate Therapy
exenatide other doses versus placebo
Moretto (DOUBLONS avec druker), 2008
NCT00381342
Exenatide 10–20 µg daily
versus
Placebo
double blind
Follow-up duration: 24 weeks
United States, Puerto Rico, Romania, Russia, India
NCT00085969,
NCT00085969
exenatide for 28 days
versus
placebo
subjects with type 2 diabetes mellitusdouble-blind
Follow-up duration: 28 days
USA
Poon, 2005
NCT00044694
exenatide at 2.5, 5.0, 7.5, or 10.0 microg administered b.i.d. for 28 days
versus
placebo
patients with type 2 diabetesdouble-blind
Follow-up duration: 28 days
exenatide other doses versus placebo (add on MER+/-SU)
Fineman, 2003
exenatide 3 regimen (0.08 micro g/kg) for 28 days
versus
placebo
patients with tyep 2 diabetes treated with diet and a sulfonylurea and/or metformindouble-blind
Follow-up duration: 28 days
USA
exenatide weekly versus insulin glargine
DURATION-3 (Diamant), 2010
NCT00641056
exenatide (2 mg, once-a-week injection)
versus
insulin glargine once-daily injection
adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longeropen (blind analysis)
Follow-up duration: 26 weeks
USA, Puerto Rico, Europe, Russia, Australia, Korea, Taiwan, Mexico
exenatide weekly versus pioglitazone
DURATION-2 (Bergenstal) (vs pioglitazone), 2010
NCT00637273
2 mg injected exenatide once weekly plus oral placebo once daily
versus
45 mg oral pioglitazone once daily plus injected placebo once weekly
double blind
Follow-up duration: 26 weeks
USA, India, and Mexico
exenatide weekly versus placebo (add on MET)
Kim, 2007
NCT00103935
exenatide LAR 0.8 or 2 µg daily
versus
Placebo on-top of metformin
subjects with type 2 diabetes suboptimally controlled with metformin and/or diet and exercisedouble blind
Follow-up duration: 15 weeks
NA
exenatide weekly versus sitagliptin
DURATION-2 (Bergenstal) (vs sitagliptin), 2010
NCT00637273
2 mg injected exenatide once weekly plus oral placebo once daily
versus
100 mg oral sitagliptin once daily plus injected placebo once weekly
patients treated with metformin double blind
Follow-up duration: 26 weeks
USA, India, and Mexico
fenofibrate versus placebo
FIELD, 2005
ISRCTN64783481
fenofibrate 200 mg daily
versus
placebo
aged 50-75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry
Follow-up duration: 5y
fenofibrate versus placebo (on top simvastatine)
ACCORD lipid, 2010
NCT00000620
fenofibrate on top simvastatin
versus
placebo (on top simvastatine)
high-risk patients with type 2 diabetes double-blind
Follow-up duration: 4.7y
United States and Canada
ACCORD lipid (subgroup Eye study), 2010
NCT00000620
fenofibrate on top simvastatin
versus
placebo (on top simvastatine)
high-risk patients with type 2 diabetes double-blind
Follow-up duration: 4.7y
United States and Canada
fluvastatin versus placebo
LIPS (sub group), 2002
fluvastatin
versus
placebo
patients (aged 18-80 years) with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dLdouble blind
Follow-up duration: 3.9y
ALERT (sub group), 2003
fluvastatin
versus
placebo
renal transplant recipients with total cholesterol 4·0–9·0 mmol/Ldouble blind
gemfibrozil versus placebo
HHS (sub group), 1987
gemfibrozil 600mg twice daily
versus
placebo
asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter double blind
VA-HIT (sub group), 1999
gemfibrozil 1200 mg per day
versus
placebo
men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less.double blind
Follow-up duration: 5.1 y
glargine versus NPH
Riddle POC 4002 Glargine, 2003
bedtime glargine
versus
NPH once daily
overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents open-label
HOE 901/3002, 2000
bedtime insulin glargine
versus
bedtime NPH insulin
insulin-naive type 2 diabetic patients with poor glycemic control on oral antidiabetic agents
glargine versus NPH + SU
Riddle ,
bedtime glargine
versus
NPH
overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents open
Follow-up duration: 24 weeks
glibenclamide versus c (add on MET)
Hermann, 1991
metformin + glibenclamide
versus
metformin
patients with non-insulin-dependent diabetes mellitus
Follow-up duration: 6 months
glibenclamide versus control (add on MET)
Marre (ass), 2002
metformin-glibenclamide 500 mg/2.5 mg or metformin-glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) < or = 7 mmol/l
versus
metformin 500 mg,
patients with Type 2 diabetes mellitus inadequately controlled by metformin monotherapydouble-blind
Follow-up duration: 16 weeks
Tosi, 2003
metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d
versus
metformin (500 to 3,000 mg/d),
double-blind
Follow-up duration: 6 months
glibenclamide versus rosiglitazone (add on MET)
Garber, 2006
metformin-glibenclamide 500/2.5 mg tablets (initial daily dose 1000/5 mg)
versus
metformin 500 mg plus rosiglitazone 4 mg (initial daily dose 1000-2000 mg + 4 mg, depending on previous treatment)
patients with type 2 diabetes inadequately controlled on metformin monotherapydouble-blind
Follow-up duration: 24 weeks
gliclazide versus nateglinide (add on MET)
Ristic, 2006
gliclazide plus metformin
versus
nateglinide plus metformin
double-blind
Follow-up duration: 52 weeks
gliclazide versus pioglitazone (add on MET)
Matthews, 2005
gliclazide 80 mg o.d. (titrated up to 320 mg
versus
pioglitazone 15 mg o.d. (titrated up to 45 mg
Patients with poorly controlled type 2 diabetes double-blind
Follow-up duration: 52 weeks
gliclazide versus rosiglitazone (add on MET)
Khanolkar, 2008
metformin and gliclazide
versus
metformin and rosiglitazone

Follow-up duration: 24 weeks
glimepiride versus glibenclamide
Draeger, 1996
glimepiride 1 mg daily
versus
2.5 mg glibenclamide
type 2 diabetic patients stabilised on glibenclamide double-blind
Protocol 311,
glimepiride 1-8mg od
versus
glibenclamide 1.75-14 mg/day (od or bid)
glimepiride versus gliclazide
Charpentier (301F),
glimepiride 1-4mg od
versus
gliclazide 80-320 mg/day (od or bid)
glimepiride versus gliclazide or glibenclamide
Inukai, 2005
glimepiride
versus
gliclazide or glibenclamide
Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SUopen
Follow-up duration: 6 months
Japan
glimepiride versus glipizide
Clark (301), 1997
glimepiride 1-16 mg/day (od or bid)
versus
glipizide 2.5-40 mg/day (od or bid)
glimepiride versus glyburide
Dills, 1996
glimepiride 1-16mg od
versus
non-micronized glyburide 1.25-20mg od
patients with non-insulin dependent diabetes double-blind
glimepiride versus placebo
Kaneko, 1993
glimepiride 0.25mg od, 0.5mg od
versus
placebo
Luis Bautista, 2003
glimepiride with titration to 2 mg and 4 mg for FPG levels >120 mg/dL
versus
placebo
Mexican American Patients with type 2 diabetes mellitusdouble-blind
Follow-up duration: 14 weeks
Mexique
Rosenstock, 1996
glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d
versus
placebo
previously treated NIDDM patientsdouble-blind
Follow-up duration: 14 weeks
Schade, 1998
glimepiride at individually determined optimal dose (1-8 mg of glimepiride) for 10+12 weeks
versus
placebo
patients with type 2 diabetes mellitus for whom diet therapy is unsuccessfuldouble-blind
Study 201 (Goldberg), 1996
glimepiride, 1, 4, or 8 mg once daily
versus
placebo
patients with NIDDMdouble-blind
Follow-up duration: 14 weeks
Study 202,
glimepiride 1-8mg od
versus
placebo
glimepiride versus placebo (add on insulin)
Riddle, 1994
Glimepiride (16 mg/day) plus insulin
versus
insulin plus placebo
obese patients with type 2 diabetes insufficiently controlled by full dosages of sulphonylureas (glimepiride titrated up to 8mg twice daily and with laboratory-monitored FPG of 10 to 16 mmol/L (180 to 300 mg/dl))
glimepiride versus placebo (add on MET)
Charpentier, 2001
metformin and glimepiride
versus
metformin
Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily double-blind
France
LEAD-2 (Nauck) Sulf vs pbo, 2009
NCT00318461
glimepiride (4 mg once daily).
versus
placebo
subjects previously treated with oral antidiabetes (OAD) therapydouble-blind
Follow-up duration: 26 weeks
glimepiride monotherapy versus metformin
Charpentier, 2001
glimepiride monotherapy
versus
metformin monotherapy
Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily for at least 4 weeks double-blind
Follow-up duration: 20 weeks
glimepiride od versus glimepiride bid
Sonnenberg, 1997
glimepirid e6mg od
versus
glimepiride 3mg bid
glipizide versus control (add on MET)
Goldstein,
glipizide/metformin 5/500 mg tablets
versus
metformin 500-mg
patients with type 2 DM that is uncontrolled by at least half the maximum labeled daily dose of a sulfonylureaopen
glipizide versus glyburide
Rosenstock, 1993
glipizide, 2.5 or 5 mg/day
versus
glyburide, 1.25 or 2.5 mg/day
elderly patients with NIDDM that was controlled for at least 3 months with oral sulfonylurea therapy open
Follow-up duration: 4 months
Birkeland, 1994
glipizide
versus
glyburide
NIDDM patients
Birkeland, 1994
glipizide
versus
glyburide
NIDDM patients double-blind
Follow-up duration: 15 months
glipizide versus placebo
Simonson, 1997
once-daily doses of 5, 20, 40, or 60 mg glipizide GITS
versus
placebo
NIDDM patientsdouble-blind
Follow-up duration: 4+8 weeks
Testa, 1998
5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS)
versus
placebo
patients with type 2 diabetes mellitus
Follow-up duration: 12 weeks
USA
Eriksson, 2006
glipizide 2.5 mg daily
versus
placebo
first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT (WHO criteria in 2006)double blind
Follow-up duration: 18 months
Finland
glipizide versus sitagliptin (add on MET)
Nauck, 2007
glipizide
versus
sitagliptin

Follow-up duration: 52 weeks
glipizide GITS versus placebo (add on MET)
Feinglos, 2005
2.5 mg glipizide GITS
versus
placebo
type 2 diabetes inadequately controlled (A1c 7-8.5%) on metformin (> or =1000 mg/day for > or =3 months)double-blind
Follow-up duration: 16 weeks
glitazone versus conventional treatment
PROactive, 2005
NCT00174993
pioglitazone titrated 15-45 mg daily
versus
standard treatment
patients with type 2 diabetes who had evidence of macrovascular diseasedouble blind
Follow-up duration: 34.5 months
19 countries
glitazone versus glimepiride
PERISCOPE, 2008
NCT00225277
pioglitazone 15 to 45 mg
versus
glimepiride, 1 to 4 mg
patients with coronary disease and type 2 diabetes double blind
Follow-up duration: 18 months
North and South America
glitazone versus glyburide
Giles, 2008
NCT00521820
pioglitazone for 6 months
versus
glyburide
patients with type 2 diabetes, systolic dysfunction, and NYHA functional Class II/III HFopen
Follow-up duration: 6 months
glulisine + glargine versus glulisine + glargine
OPAL, 2008
single injection of glulisine before breakfast
versus
single injection of glulisine before their main mealtime (breakfast, lunch or dinner);
patients with type 2 diabetes who were suboptimally controlled on their previous glargine and OAD regimen
glyburide versus c (add on MET)
DeFronzo, 1995
metformin and glyburide
versus
metformin
patients with non-insulin-dependent diabetes mellitus double-blind
Follow-up duration: 29 weeks
USA
Erle, 1999
low-dose glyburide plus metformin
versus
high-dose glyburide alone
glyburide versus control (add on MET)
Blonde, 2002
glyburide/metformin 2.5 mg/500 mg (n = 160); or glyburide/metformin 5 mg/500 mg (n = 162)
versus
metformin 500 mg
patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea double-blind
Follow-up duration: 16 weeks
Garber, 2003
glyburide/metformin
versus
metformin
patients with type 2 diabetes who had inadequate glycemic control [glycosylated hemoglobin A(1C) (A1C), >7% and <12%) with diet and exercise alone
glyburide versus placebo
Garber, 2002
glyburide 2.5 mg
versus
placebo
patients with type 2 diabetes who had failed diet and exercisedouble-blind
Vray, 1995
glibenclamide (2.5 mg X 3/d)
versus
placebo
type 2 diabetic outpatients, 40-70 years of age, treated by diet alone or oral anti-diabetic drugsdouble-blind
China
insulin versus control
UGDP,

versus
UKPDS 33,

versus
insulin aspart at mealtimes versus NPH insulin once daily
Gram, 2011
insulin aspart at mealtimes
versus
NPH insulin once daily at bedtime
insulin detemir versus glargine
Fadini, 2011

versus
insulin detemir versus NPH insulin
Hermansen ,
insulin detemir twice-daily
versus
NPH insulin
insulin-naive people with type 2 diabetes
Follow-up duration: 26 weeks
insulin glargine versus control
ORIGINE, 2012
NCT00069784
insulin glargine (with a target fasting blood glucose level of ¡Ü95 mg per deciliter
versus
standard care
with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes
Follow-up duration: 6.2 years
insulin glargine versus placebo
GRACE - ORIGIN (glargine), 2012
insulin glargine (with a target fasting blood glucose level of <=95 mg per deciliter [5.3 mmol per liter])
versus
standard glycemic care alone
subject with known CV disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetesopen-label
insulin glargine plus insulin glulisine versus premixed insulin analogues
Levin, 2011

versus
insulin glulisine + glargine versus glargine once daily
Owens, 2011
basal+bolus (single dose of insulin glulisine immediately prior to the main meal)
versus
basal insulin (glargin)
patients withT2DM using any basal insulin and HbA1c >7.0% after 3-month of insulin glargine titrated to optimize fasting bloodglucose controlopen-label
Follow-up duration: 3 months
US, UK, Russia
insulin lispro protamine suspension plus lispro versus glargine plus lispro
Koivisto, 2011

versus
intensive versus usual
ABCD normotensives, 1993
intensive (10 mm Hg below the baseline DBP) DBP control
versus
moderate (80 to 89 mm Hg) DBP control
normotensive type 2 diabetic patientsopen
Follow-up duration: 5.3 y
ACCORD (blood pressure), 2010
NCT00000620
intensive blood-pressure control, targeting a systolic pressure of less than 120 mm Hg
versus
standard blood-pressure control
high-risk patients with type 2 diabetes, high HbA1c concentrations (>7.5%), and cardiovascular disease (or >=2 cardiovascular risk factors)open
Follow-up duration: 4.7 y
United States, Canada
HOT <=80 (diabetic subgroup), 1998
target diastolic blood pressure <=80 mmHg
versus
target diastolic blood pressure <=90 mmHg
patients aged 50-80 years with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg; diabetics subgroupopen
Follow-up duration: 3.8y
26 countries
intensive dietary advice versus routine dietary advice
Wein, 1999
intensive dietary advice
versus
routine dietary advice
women with previous gestational diabetes and currently with impaired glucose tolerance (WHO 1985 criteria)open
Follow-up duration: 4.24 y
USA
intensive glycemic control versus conventional treatment
UGDP (insulin), 1982
intensive insulin
versus
standard insulin
patient with non insulin-dependent adult onset diabetes open
Follow-up duration: >5 years
ACCORD, 2008
NCT00000620
very intensive glycemic control through currently available means (targetinga glycosylated hemoglobin <6%) during a mean of 3.7 years
versus
standard glycemic control (targeting a glycosylated hemoglobin 7.0-7.9%)
patients with type 2 diabetes mellitus at high risk of death and stroke (pre-existing heart disease or two or more additional risk factors for heart disease)open
Follow-up duration: 3.5y (5y)
USA, Canada
ADDITION, 2010
NCT00237549
intensive multifactorial treatment
versus
routine care
patients with newly diagnosed type 2 diabetes open
Follow-up duration: 5 year
Denmark, United Kingdom, the Netherlands
ADVANCE, 2008
NCT00145925
intensive glucose-lowering treatments HbA1C <=6.5% using gliclazide(modified release) plus other drugs
versus
standard glucose-lowering treatments (targetglycated hemoglobin levels defined on the basisof local guidelines)
patients with type 2 diabetesopen
Follow-up duration: median 5 y
20 countries
Kumamoto (primary prev), 1995
intensive glycemic control with multiple insulin injection treatment
versus
conventional insulin injection treatment (1-2 daily injections)
patients with non-insulin-dependent diabetes mellitus and with no retinopathy and urinary albumin excretions < 30 mg/24 hopen
Follow-up duration: 8.0y
Japan
Kumamoto (secondary prev), 1995
multiple insulin injection treatment
versus
conventional insulin injection treatment (1-2 daily injections)
patients with non-insulin-dependent diabetes mellitus and simple retinopathy open
Follow-up duration: 8.0y
Japan
Steno 2, 2003
targeted, intensified, multifactorial intervention
versus
conventional treatment on modifiable risk factors for cardiovascular disease
patients with type 2 diabetes and microalbuminuriaopen
Follow-up duration: 7.8 y
Denmark
UKPDS 33, 1998
intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin; fasting plasma glucose <6.0 mmol/L
versus
conventional policy with diet
newly diagnosed patients with type 2 diabetes who after 3 months’ diet treatment had a mean of two fasting plasma glucose concentrations of 6·1–15·0 mmol/Lopen
Follow-up duration: 10.3 y
UK
VA CSDM, 1997
intensive glycemic control(stepped plan from 1 evening injection of insulin, alone or with glipizide, to multiple daily injections, target to attain near-normal glycemia levels)
versus
standard treatment (1 insulin injection every morning)
non-insulin-dependent diabetes mellitus patientsopen
Follow-up duration: 2.3y
USA
VADT, 2008
NCT00032487
intensive glucose control
versus
standard glucose control
military veterans who had a suboptimal response to therapy for type 2 diabetesopen
Follow-up duration: 5.6y
US
irbesartan versus amlodipine
IDNT (irbesartan vs amlodipine), 2001
Irbesartan 300 mg daily
versus
amlodipine 10 mg daily
hypertensive patients with nephropathy due to type 2 diabetes double blind
Follow-up duration: 2.6 years
Worldwide
irbesartan versus placebo
IDNT (irbesartan vs pbo), 2001
Irbesartan 300 mg daily
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetes double blind
Follow-up duration: 2.6 years
Worldwide
IPDM (150mg), 2001
irbesartan 150 mg daily
versus
placebo
hypertensive patients with type 2 diabetes and microalbuminuriadouble-blind
Follow-up duration: 2 years
Worldwide
jiangtang bushen recipe versus control
Fan, 2004
jiangtang bushen recipe 2-3 times/week
versus
placebo
patients with impaired glucose tolerance (WHO 1999 criteria)open
Follow-up duration: 4.1 y
China
lifestyle modification versus control
DPS (Lindström), 2003
individualized counseling aimed at reducing weight and intake of total and saturated fat, and increasing intake of fiber and physical activity
versus
control
Patients overweight with impaired glucose tolerance (WHO 1985 criteria)open
Follow-up duration: 3.2y
Finnish
Fang, 2004
standard prevention education
versus
subject with impaired glucose tolerance
China
JDPP (Sakane), 2005
lifestyle intervention
versus
patients with impaired glucose tolerance (WHO 1999 criteria)
Japan
Keen, 1982
either dietary teaching to restrict carbohydrate intake to 120 g/day or advice to restrict table sugar
versus
subject with impaired glucose tolerance
Kosaka, 2005
to maintain body mass index (BMI) of <24.0 kg/m2 and of <22.0 kg/m2, respectively, by diet and exercise. In the intervention group, detailed instructions on lifestyle were repeated every 3-4 months
versus
control
men with impaired glucose tolerance (WHO criteria 1980)open
Follow-up duration: 3.64 y
Japan
Pan, 1997
three active treatment groups: diet only, exercise only, or diet plus exercise
versus
control
Patients with impaired glucosetolerance (WHO 1985 criteria)open
Follow-up duration: 6 y
China
Tao, 2004
lifestyle intervention
versus
patients with impaired glucose tolerance (WHO 1999 criteria)
Follow-up duration: 31 months
China
US-DDP (lifestyle) (Knowler), 2002
lifestyle-modification intervention
versus
placebo
nondiabetic patients with elevated glucose and high risk for diabetesopen
Follow-up duration: 2.8 years
lifestyle modification + metformin versus control
IDDP (Ramachandran), 2006
advice on lifestyle modification, metformin, or both
versus
given standard health care advice (control)
native Asian Indians with impaired glucose toleranceopen
Follow-up duration: 2.5 y
India
Jarret, 1979
carbohydrate restriction with phenformin 50 mg daily
versus
carbohydrate restriction alone
men with impaired glucose tolerancopen
Follow-up duration: 4.3 y
linagliptin versus glimepiride
CAROLINA, 2012
NCT01243424
linagliptin
versus
glimepiride 1-4 mg QD
patients with type 2 diabetes at elevated cardiovascular risk receiving usual caredouble-blind
Follow-up duration: 2 years
USA
linagliptin versus glimepiride (add on MET)
Gallwitz, 2012
NCT00622284
linagliptin (5 mg once daily) add-on therapy to preferably > 1500 mg metformin
versus
glimepiride (1—4 mg) orally once daily add-on therapy to preferably > 1500 mg metformin
type 2 diabetes mellitus with insufficient glycaemic control with metformindouble-blind
Follow-up duration: 104 weeks
USA
linagliptin versus Metformin + sulfonylurea
Owens, 0
NCT00602472
linagliptin
versus
combination of metformin and an SU
type 2 diabetes mellitus with insufficient glycaemic control with metformin in combination with a sulphonylurea
Follow-up duration: 24 weeks
Argentina
linagliptin versus placebo
Del Prato, 0
NCT00621140
Linagliptin monotherapy
versus
placebo
Type 2 Diabetic Patients With Insufficient Glycemic Control double-blind
Follow-up duration: 24 weeks
Croatia
linagliptin versus placebo (add on MET)
Taskinen, 0
NCT00601250
linagliptin 5 mg once daily
versus
placebo add on MET
patients with inadequately controlled type 2 diabetes for whom metformin therapy is inappropriate due to intolerability or contraindication
linagliptin versus placebo (add on pioglitazone)
Gomis, 2011
NCT00641043
initial combination of 30 mg pioglitazone plus 5 mg linagliptin
versus
pioglitazone plus placebo
patients with inadequately controlled type 2 diabetes
Follow-up duration: 24 weeks
linagliptin versus placebo (add on SU)
Lewin, 2010
NCT00819091
linagliptin 5 mg
versus
placebo (add-on to sulphonylurea)
patients with type 2 diabetes and insufficient glycaemic control double-blind
Follow-up duration: 18 weeks
liraglutide versus placebo
LEADER, 2016
NCT01179048
Maximum dose of 1.8 mg liraglutide, injected subcutaneously once daily
versus
placebo
subjects with type 2 diabetesdouble-blind
Follow-up duration: 3.8 years (median)
Africa, Asia, Europe, North and South America
liraglutide 1.2mg versus glimepiride
LEAD-3 mono 1.2mg (Garber), 2009
NCT00294723
liraglutide 1.2 mg daily
versus
glimepiride 8 mg once daily
patients with early type 2 diabetes double blind
Follow-up duration: 52 weeks (104 weeks)
North America, Mexico
liraglutide 1.2mg versus glimepiride (add on MET)
LEAD-2 (Nauck) (1.2 mg vs glimepiride), 2009
NCT00318461
Liraglutide 1.2mg daily for 26 weeks
versus
Glimepiride on-top of Metformin
patients with type 3 diabetes previously treated with oral antidiabetes (OAD) therapdouble blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.2mg versus placebo (add on MET)
LEAD-2 (Nauck) (1.2mg vs placebo), 2009
NCT00318461
Liraglutide 1.2 mg daily
versus
Placebo on-top of Metformin
subjects previously treated with oral antidiabetes therapy double blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.2mg versus placebo (add on SU)
LEAD-1 SU (1.2 mg vs placebo), 2009
NCT00318422
Liraglutide 1.2 mg daily
versus
Placebo on-top of sulphonylureas
subjects with Type 2 diabetes double-blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.2mg versus placebo (add on TZD+MET)
LEAD-4 (1.2mg), 2009
NCT00333151
Liraglutide 1.2 daily
versus
Placebo on-top of thiazolidinediones + metformin
patients with type 2 diabetes, A1C 7–11% (previous OAD monotherapy >=3 months) or 7–10% (previous OAD combination therapy >=3 months), and BMI 45 kg/m2double-blind
Follow-up duration: 26 weeks
USA, Canada
liraglutide 1.2mg versus rosiflitazone
LEAD-1 SU (1.2 vs rosiglitazone), 2009

versus
liraglutide 1.2mg versus sitagliptin
Pratley 1.2mg, 2010
NCT00700817
liraglutide 1.2mg subcutaneously once daily
versus
oral sitagliptin 100mg once daily
patients with type 2 diabetes who did not have adequate glycemic control with metforminopen
Follow-up duration: 26 weeks
Europe, USA, Canada
liraglutide 1.8mg versus exenatide on top MET/SU/MET+SU
LEAD-6, 2009
NCT00518882
liraglutide 1.8 mg once a day
versus
exenatide 10 microg twice a day
Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or bothopen
Follow-up duration: 26 weeks
15 countries
liraglutide 1.8mg versus glimepiride
LEAD-3 mono 1.8mg (Garber), 2009
NCT00294723
liraglutide 1.8 mg daily
versus
glimepiride 8 mg once daily
subjects with type 2 diabetes double blind
Follow-up duration: 52 weeks (104 weeks)
North America, Mexico
liraglutide 1.8mg versus glimepiride (add on MET)
LEAD-2 (Nauck) (1.8 mg vs glimepiride), 2009
NCT00318461
Liraglutide 1.8 mg daily for 26 weeks
versus
Glimepiride on-top of Metformin
patients with type 3 diabetes previously treated with oral antidiabetes (OAD) therap double blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.8mg versus insulin glargine (add on SU+MET)
LEAD-5 (vs Glargine), 2009
NCT00331851
Liraglutide 1.8 mg daily
versus
Glargine on-top of sulphonylureas+metformin
adult patients with type 2 diabetesopen
Follow-up duration: 26 weeks
17 countries
liraglutide 1.8mg versus liraglutide 1.2mg
LEAD 1 (1.8 vs 1.2), 2009

versus
LEAD 2 (1.8 vs 1.2), 2009

versus
LEAD 4 (1.8 vs 1.2), 2009

versus
Pratley (1.8 vs 1.2), 2010

versus
liraglutide 1.8mg versus placebo (add on MET)
LEAD-2 (Nauck) (1.8mg vs placebo), 2009
NCT00318461
Liraglutide 1.8 mg daily
versus
Placebo on-top of Metformin
subjects previously treated with oral antidiabetes therapy double blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.8mg versus placebo (add on SU)
LEAD-1 SU (1.8 mg vs placebo), 2009
NCT00318422
Liraglutide 1.8 mg daily
versus
Placebo on-top of sulphonylureas
patients with type 2 diabetes double-blind
Follow-up duration: 26 weeks
21 countries
liraglutide 1.8mg versus placebo (add on SU+MET)
LEAD-5 (vs placebo), 2009
NCT00331851
Liraglutide 1.8 mg daily
versus
Placebo on-top of sulphonylureas+metformin
adult patients with type 2 diabetes double-blind
Follow-up duration: 26 weeks
17 countries
liraglutide 1.8mg versus placebo (add on TZD+MET)
LEAD-4 (1.8mg), 2009
NCT00333151
Liraglutide 1.8 daily
versus
Placebo on-top of thiazolidinediones + metformin
patients with type 2 diabetes, A1C 7–11% (previous OAD monotherapy >=3 months) or 7–10% (previous OAD combination therapy >=3 months), and BMI 45 kg/m2 double-blind
Follow-up duration: 26 weeks
USA, Canada
liraglutide 1.8mg versus sitagliptin
Pratley 1.8mg, 2010
NCT00700817
liraglutide 1.8mg subcutaneously once daily
versus
oral sitagliptin 100mg once daily
patients with type 2 diabetes who did not have adequate glycemic control with metformin open
Follow-up duration: 26 weeks
Europe, USA, Canada
liraglutide other doses versus glibenclamide
Seino, 2010
NCT00393718
liraglutide 0.9 mg once daily
versus
glibenclamide once or twice daily at a planned maximum dose of 2.5 mg/day, before or after meals
Japanese subjects with type 2 diabetes, inadequately controlled with diet therapy or oral antidiabetic drug monotherapydouble-blind
Follow-up duration: 24-week
Japan
liraglutide other doses versus glimepiride
Madsbad (vs Glimepiride), 2004
Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily
versus
Glimepiride
Outpatients with type 2 diabetesopen
Follow-up duration: 12 weeks
UK, Scandinavia
liraglutide other doses versus metformin
Feinglos, 2005
Liraglutide 0.045, 0.225, 0.45, 0.6 or 0.75 mg daily for 12 weeks
versus
metformin 1000mg twice daily
subjects with Type 2 diabetesdouble blind (not adequate)
Follow-up duration: 12 weeks
liraglutide other doses versus placebo
Harder, 2004
single daily subcutaneous dose of 0.6 mg liraglutide for 8 weeks
versus
placebo
obese subjects with type 2 diabetesdouble-blind
Follow-up duration: 8 weeks
Denmark
Kaku 0.6mg, 2010
liraglutide 0.6 mg/day
versus
placebo
Japanese patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
Japan
Madsbad (vs placebo), 2004
Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily
versus
Placebo
Outpatients with type 2 diabetes open
Follow-up duration: 12 weeks
UK, Scandinavia
NN2211-1571 (Vilsbøll), 2007
NCT00154401
liraglutide 0.65 mg, 1.25 mg or 1.9 mg for 14 weeks
versus
placebo
subjects with type 2 diabetes double-blind
Follow-up duration: 14 weeks
Denmark, France, Slovakia, Netherlans
Seino, 2008
NCT00154414
Liraglutide 0.1, 0.3, 0.6 or 0.9 mg once daily for 14 weeks
versus
Placebo
Japanese subjects with type 2 diabetes double blind
Follow-up duration: 14 weeks
Japan
liraglutide other doses versus placebo (add on MET)
NN2211-1796, 0
NCT00614120
liraglutide added to metformin
versus
glimepiride added to metformin

China
liraglutide other doses versus placebo (on top SU)
Kaku 0.9mg, 2010
liraglutide 0.9 mg/day
versus
placebo
Japanese patients with type 2 diabetes double-blind
Follow-up duration: 24 weeks
Japan
liraglutide other doses versus rosiglitazone (add on SU)
LEAD-1 SU (1.8 vs rosiglitazone), 2009
NCT00318422
Liraglutide 0.6, 1.2 or 1.8 mg daily
versus
rosiglitazone on-top of sulphonylureas
double-blind
Follow-up duration: 26 weeks
21 countries
lisinopril versus chlorthalidone
ALLHAT (lisi vs chlor, diabetic subgroup), 2002
lisinopril 10 to 40 mg/d
versus
chlorthalidone 12.5 to 25 mg/d
diabetic (subgroup) participants aged 55 years or older with hypertensiondouble-blind
Follow-up duration: 4.9 y
lispro versus glargine once-daily
APOLLO (Bretzel), 2008
NCT00311818
nsulin lispro administered three times per day
versus
insulin glargine taken once daily at the same time every day
type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents
lispro versus insulin detemir
Fogelfeld, 2010
Insulin lispro protamine suspension
versus
insulin detemir once daily at bedtime
insulin-naive patients with Type 2 diabetesopen-label
Follow-up duration: 24 week
lispro + NPH versus NPH + SU
Bastyr, 1999
preprandial insulin lispro plus bedtime NPH insulin
versus
bedtime neutral protamine Hagedorn (NPH) insulin plus sulfonylurea
lispro + NPH versus NPH twice daily
Ceriello, 2007
premeal insulin lispro+bedtime neutral protamine Hagedorn (NPH)
versus
twice-daily NPH
patients with type 2 diabetes treated by a 2-month lead-in with twice-daily NPH treatmentopen-label
Follow-up duration: 12 weeks
lispro +glargine versus continuous infusion
Herman, 2005
multiple daily injection using insulin lispro and insulin glargine
versus
continuous subcutaneous insulin infusion using insulin lispro
lispro insulin versus NPH insulin
Bastyr, 2000
insulin lispro
versus
bedtime NPH insulin
lispro insulin + NPH insulin versus regular insulin + NPH insulin
Altuntas, 2003
lispro insulin + NPH insulin
versus
regular insulin + NPH insulin
lispro mixture versus glargine once daily
Chan META-ANALYSIS, 2009
insulin lispro mixtures, given twice or thrice daily
versus
insulin glargine, given once daily
patients with type 2 diabetes treated with metformin
lispro PS versus glargine
Strojek, 2010
insulin lispro protamine suspension (ILPS) once or twice daily
versus
insulin glargine once daily
open-label
lispro thrice daily versus basal insulin
Raz, 2009
three premeal doses of insulin lispro
versus
NPH twice daily or insulin glargine once daily
patients with type 2 diabetes after acute myocardial infarction
lispro twice daily + NPH insulin versus regular insulin + NPH insulin
Vignati, 0
twice-daily insulin lispro in combination with NPH human insulin
versus
regular human insulin in combination with NPH human insulin
lixisenatide versus glargine once daily
GETGOAL-L, 0
NCT00715624
AVE0010 (10,15 and 20 µg) in association with basal insulin, with or without metformin
versus
placebo on top basal insulin
Type 2 diabetes mellitus insufficiently controlled with basal insulin with or without metformindouble-blind
Follow-up duration: 24 weeks
USA
lixisenatide versus placebo
ELIXA,
NCT01147250
lixisenatide
versus
placebo
patients with T2DM and a recent ACS eventdouble-blind
Follow-up duration: 25 months (median)
49 countries
lixisenatide versus placebo (add on basal insulin)
GETGOAL-L, 0
NCT00715624
AVE0010 (10,15 and 20 µg) in association with basal insulin, with or without metformin
versus
placebo on top basal insulin
Type 2 diabetes mellitus insufficiently controlled with basal insulin with or without metformindouble-blind
Follow-up duration: 24 weeks
USA
lixisenatide versus placebo (add on MET)
Ratner DRI6012, 2010
NCT00299871
subcutaneous lixisenatide doses of 5, 10, 20 or 30 microg once daily or twice daily
versus
placebo
patients with Type 2 diabetes inadequately controlled with metformin (>= 1000 mg/day)double-blind (nature not volume)
Follow-up duration: 13 weeks
multinational
losartan versus atenolol
LIFE (diabetic subgroup), 2002
losartan 50mg daily at step 1
versus
atenolol 50mg daily at step 1
patients with diabetes (subgroup) , hypertension, and signs of left-ventricular hypertrophy on electrocardiogramsdouble-blind
Follow-up duration: 4.7 years
USA, UK, Nordic countries
losartan versus placebo
RENAAL, 2001
losartan 50 to 100 mg once daily
versus
placebo
patients with type 2 diabetes and nephropathydouble-blind
Follow-up duration: 3.4 y
America, Europe, Asia
lovastatin versus placebo
AFCAPS/TexCAPS (sub group), 1998
lovastatin
versus
placebo
men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levelsdouble blind
metformin versus Acarbose
Maji vs acarbose,
500
versus
Acarbose

Follow-up duration: 156
metformin versus control
James, 2005
metformin 1 g BID
versus
no treatment
Abdominal obesity with insulin resistance[
Follow-up duration: 8 weeks
metformin versus Glibenclamide
Yki-Yarvinen vs glibenclamide, 1999
2.000
versus
Glibenclamide

Follow-up duration: 52
Kahn (ADOPT) vs glibenclamide,
2.000
versus
Glibenclamide

Follow-up duration: 208
metformin versus Glimepiride
Yamanouchi vs glimepiride, 2005
750
versus
Glimepiride

Follow-up duration: 52
metformin versus Glipizide
Campbell, 1994
1.000
versus
Glipizide

Follow-up duration: 52
Stakos vs glipizide,
500
versus
Glipizide

Follow-up duration: 104
metformin versus Glipizide/
Vahatalo vs glipizide/glimepiride,
2.500-
versus
Glipizide/

Follow-up duration: 52
metformin versus glyburide
ADOPT, 2006
NCT00279045
metformin,
versus
glyburide
recently diagnosed type 2 diabetes
Follow-up duration: 4 years (median)
metformin versus Insulin
Yki-Yarvinen vsinsulin,
2.000
versus
Insulin

Follow-up duration: 52
Klein, 1991
2.550
versus
Insulin

Follow-up duration: 52
Barnett, 2008
NR
versus
Insulin

Follow-up duration: 128
metformin versus None
Vahatalo vs control, 2007
2.500
versus
None

Follow-up duration: 52
Maji vs control, 2005
500
versus
None

Follow-up duration: 156
UKPDS 34 vs control,
2.550
versus
None

Follow-up duration: 556
UKPDS 34 bis,
2.550
versus
None

Follow-up duration: 343
Zhang,
750
versus
None

Follow-up duration: 76
Ramachandran,
500
versus
None

Follow-up duration: 156
metformin versus Pioglitazone
Yamanouchi vs pioglitazone, 0
750
versus
Pioglitazone

Follow-up duration: 52
Shernthaner, 2004
2.000
versus
Pioglitazone

Follow-up duration: 52
Derosa, 2009
3.000
versus
Pioglitazone

Follow-up duration: 64
Charbonnel, 2005
2.550
versus
Pioglitazone

Follow-up duration: 104
metformin versus placebo
Baillargeon, 2004
metformin 850 mg BID
versus
placebo
Non obese women with PCOS
Follow-up duration: 26 weeks
Hermann, 2001
metformin 1.700
versus
Placebo
obese and overweight type 2 diabetes patients treated with insulin for at least 1 year, and with poor glycaemic control (HbA1c > upper reference level + 2%)double-blind
Follow-up duration: 52 weeks
Bridger, 2006
metformin 750 mg BID
versus
placebo
Adolescents with PCOS and insulin resistance
Follow-up duration: 12 weeks
Charles, 1998
metformin 850 mg BID
versus
placebo
Abdominal obesity
Follow-up duration: 52 weeks
Charles, 2000
metformin 850 mg BID
versus
placebo
Abdominal obesity, hypertension, and elevated triglycerides
Follow-up duration: 13 weeks
Choux, 2003
metformin 500 mg TID
versus
placebo
PCO
Follow-up duration: 13 weeks
Crave, 1995
metformin 850 mg BID
versus
placebo
Overweight with PCO
Follow-up duration: 17 weeks
EDIT (Holman), 2003
metformin 500 mg three times/day,
versus
placebo
(WHO 1985 criteria)
UK
Douek, 2005
2.000
versus
Placebo

Follow-up duration: 52
HOME, 2009
NCT00375388
metformin 850 mg
versus
placebo
patients with DM2 treated with insulindouble-blind
Follow-up duration: 4.3 y
The Netherlands
Fleming, 2002
metformin 850 mg BID
versus
placebo
PCO
Follow-up duration: 17 weeks
Gregorio, 1999
1.700
versus
Placebo

Follow-up duration: 76
Freemark, 2001
metformin 500 mg BID
versus
placebo
Insulin resistance and family history of diabetes
Follow-up duration: 26 weeks
Teupe, 1991
1.700
versus
Placebo
Type 2 diabetic patientsopen
Follow-up duration: 104
Canada
Gambineri, 2004
metformin 850 mg BID
versus
placebo
Obesity and PCOS
Follow-up duration: 26 weeks
Giugliano, 1993
metformin 850 mg BID
versus
placebo
Hypertension with normal glucose tolerance
Follow-up duration: 12 weeks
Hoeger, 2004
metformin 850 mg BID + lifestyle modification
versus
placebo + lifestyle modification
Overweight with PCOSo[
Follow-up duration: 48 weeks
Kooy (HOME), 2009
2.000
versus
Placebo
Patients with type 2 diabetes double blind
Follow-up duration: 220
Kay, 2001
metformin 850 mg BID
versus
placebo
Adolescents with morbid obesity
Follow-up duration: 8 weeks
Kelly, 2002
metformin 500 mg TID
versus
placebo
PCO
Follow-up duration: 26 weeks
Kocak, 2002
metformin 850 mg BID
versus
placebo
PCO
Follow-up duration: 8 weeks
Lehtovirta, 2001
metformin 500 mg BID
versus
placebo
Overweight with impaired glucose tolerance and family history of diabetes
Follow-up duration: 26 weeks
palomba,
1.700
versus
Placebo

Follow-up duration: 52
Ibanez,
850
versus
Placebo

Follow-up duration: 52
Harborne,
1.500
versus
Placebo

Follow-up duration: 52
Li, 1999
metformin 250 mg three times/day
versus
placebo
patients with impaired glucose tolerance (WHO 1985 criteria)double blind
Follow-up duration: 12 months
China
Li,
2.000
versus
Placebo

Follow-up duration: 52
Moghetti, 2000
metformin 500 mg TID
versus
placebo
PCOS with normal glucose tolerance
Follow-up duration: 26 weeks
Martinez,
1.700
versus
Placebo

Follow-up duration: 52
Morel, 1999
metformin 850 mg BID
versus
placebo
Impaired glucose tolerancee
Follow-up duration: 8 weeks
Gambineri,
1.700
versus
Placebo

Follow-up duration: 52
Lund,
2.000
versus
Placebo

Follow-up duration: 52
BIGPRO (Charles),
1.700
versus
Placebo

Follow-up duration: 52
Ng, 2001
metformin 500 mg TID
versus
placebo
PCO
Follow-up duration: 12 weeks
Orchard, 2005
metformin 850 mg BID
versus
placebo
Impaired glucose tolerance
Follow-up duration: 156 weeks
Stakos vs placebo,
500
versus
Placebo

Follow-up duration: 104
Shuster,
500
versus
Placebo

Follow-up duration: 104
Pasquali, 2000
metformin 850 mg BID
versus
placebo
Abdominal obesity with and without PCO
Follow-up duration: 26 weeks
DPP (Knowler),
1.700
versus
Placebo

Follow-up duration: 156
Ibanez 62, 0
425
versus
Placebo

Follow-up duration: 208
Rodriguez, 2004
metformin 1.7 g/d
versus
placebo
Obesity with insulin resistance
Follow-up duration: 20 weeks
Rodriguez-Moctezuma, 2004
metformin 850 mg BID
versus
placebo
Family history of diabetes
Follow-up duration: 8 weeks
Sirtori, 1984
metformin 850 mg BID
versus
placebo
Peripheral vascular disease
Follow-up duration: 26 weeks
Srinivasan, 2006
metformin 1 g BID
versus
placebo
Children and adolescents with obesity and insulin resistance
Follow-up duration: 26 weeks
Stakos, 2005
metformin 500 mg/d
versus
placebo
African-Americans with insulin resistance and family history of diabetes
Follow-up duration: 104 weeks
Sturrock, 2002
metformin 1500 mg/d
versus
placebo
PCO
Follow-up duration: 13 weeks
Tang, 2006
metformin 850 mg BID
versus
placebo
Obesity with PCO
Follow-up duration: 26 weeks
US-DPP (metformin) (Knowler), 2002
metformin 850mg twice daily
versus
placebo
nondiabetic patients with elevated glucose and high risk for diabetesdouble blind
Follow-up duration: 2.8 years
USA
Vitale, 2005
metformin 500 mg BID
versus
placebo
Metabolic syndrome
Follow-up duration: 13 weeks
metformin versus Rosiglitazone
maji vs rosiglitazone,
500
versus
Rosiglitazone

Follow-up duration: 156
ADOPT vs rosiglitazone,
2.000
versus
Rosiglitazone

Follow-up duration: 208
RECORD,
2.550
versus
Rosiglitazone

Follow-up duration: 260
Tomazic,
1.000
versus
Rosiglitazone

Follow-up duration: 52
metformin versus SU/Insulin
UKPDS (vs SU or INS), 0
2.550
versus
SU/Insulin
Type 2 diabetic patientsopen
Follow-up duration: 556
UK
metformin versus Vildagliptin
Schweizer, 2007
2.000
versus
Vildagliptin

Follow-up duration: 52
metformin + repaglinide versus repaglinide
AGEE-1411, 0
NCT01465152
metformin and repaglinide
versus
repaglinide
subjects with type 2 diabetes in which diet and exercise have failedopen
Follow-up duration: 24 weeks
Spain
metoprolol versus placebo
MERIT-HF, 2005
metoprolol CR/XL
versus
placebo
patients with CHF NYHA classe 2 to 4 and EF<=40% sub group of diabetic patientsdouble-blind
Follow-up duration: 1y
USA and Europe
miglitol versus placebo (add on to met)
Van Gaal, 2001
miglitol force-titrated: 4 weeks at 25 mg miglitol t.i.d., 12 weeks at 50 mg miglitol t.i.d., and 16 weeks at 100 mg miglitol t.i.d.
versus
placebo
type 2 diabetic outpatients insufficiently controlled (HbA1c between 7.5 and 10.5%) with diet and metformindouble-blind
Follow-up duration: 32 weeks
mitiglinide versus nateglinide
Gao, 0
NCT00461617
mitiglinide 10 - 20 mg three times daily
versus
nateglinide 120 mg three times daily
Chinese type 2 diabetes mellitus patients double-blind
Follow-up duration: 20 weeks
mitiglinide versus on top insulin glargine
Kumashiro, 2007
mitiglinide
versus
on top of once daily insulin glargine
mitiglinide versus placebo (add on MET)
NCT01037842,
NCT01037842
mitiglinide
versus
placebo
patients with type 2 diabetes who show inadequate glycemic control with metformin monotherapydouble-blind
Follow-up duration: 16 weeks
Korea
EX-1510-CT-003, 0
NCT00519142
metformin + mitiglinide three times a day with meals
versus
(metformin + placebo for mitiglinide
patients with Type 2 diabetes mellitus not well controlled with metformin alonedouble-blind
Follow-up duration: 24 weeks
US
mitiglinide versus placebo (on top pioglitazone)
Kaku, 2009
additional mitiglinide 5 or 10 mg tid
versus
placebo on top pioglitazone
Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapymulticenter
Follow-up duration: 16 weeks
mitiglinide+voglibose versus insulin glargine
GLORIA, 0
NCT00663884
combination therapy of 10 mg mitiglinide or 0.2mg voglibose
versus
insulin glargine
diabetic patients whose glycemic control were not enough despite administration of oral antidiabetic drug or insulin glargineopen
Follow-up duration: 16 weeks
Korea
Mix 25/75 versus glargine once-daily
Roach, 2006
insulin lispro mixture (25% insulin lispro and 75% NPL; Mix 25/75) twice-daily plus oral glucose-lowering medications (metformin and/ or sulphonylurea)
versus
once-daily insulin glargine plus oral agents
patients with Type 2 diabetes inadequately controlled with insulin and/or oral glucose-lowering agents
more intensive blood pressure lowering strategie versus less intensive blood pressure lowering strategie
ABCD target (H) , 2000
intensive treatment with a diastolic blood pressure goal of 75 mmHg
versus
moderate treatment with a diastolic blood pressure goal of 80-89 mmHg
diabetes patients with DBP >=90 mmHgopen
Follow-up duration: 5 year
ABCD target (N) , 2002
intensive treatment (diastolic blood pressure decrease of 10 mmHg below baseline DBP)
versus
moderate treatment (diastolic blood pressure goal of 80-89 mmHg)
diabetes patients with diastolic blood pressure between 80 and 89mmHgopen
morning insulin glargine versus bedtime insulin glargine
Fritche ,
morning insulin glargine
versus
bedtime insulin glargine
patients with type 2 diabetes previously treated with oral antidiabetic agentsopen
Follow-up duration: 24 weeks
n-3 fatty acid supplement versus placebo
GRACE - ORIGIN (n-3 fatty acid),
n-3 fatty acid supplemen
versus
placebo
subjects with known CV disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetesdouble-blind
Follow-up duration: 4.9y (median)
nateglinide versus glibenclamide (add on MET)
Derosa , 2009
nateglinide
versus
glibenclamide
naïve type 2 diabetic patients treated with metformindouble-blind
Follow-up duration: 12 months
nateglinide versus gliclazide (add on MET)
Ristic, 2006
nateglinide plus metformin
versus
gliclazide plus metformin
Patients with inadequate glucose control on maximal doses of metformindouble-blind
Follow-up duration: 24 weeks
nateglinide versus glyburide (add on MET)
PRESERVE-beta,

versus
nateglinide versus placebo
CDJN608AUS13 ,

versus
CDJN608AUS13 ,

versus
CDJN608A ES03,

versus
NAVIGATOR,

versus
patients with impaired glucose toler-ance (IGT)
Schwarz , 2008
nateglinide monotherapy (120 mg, before meals)
versus
placebo
drug-naïve patients with T2DM aged >or=65 yearsdouble-blind
Follow-up duration: 12 weeks
Schwarz (study 2), 2008
nateglinide monotherapy (120 mg, before meals)
versus
drug-naïve patients with T2DM aged >or=65 years double-blind
Follow-up duration: 12 weeks
NAVIGATOR nateglinide, 2010
NCT00097786
nateglinide 60mg 3 times daily
versus
placebo
subjects with impaired glucose tolerance and either CV disease or CV risk factors double-blind
Follow-up duration: 5 years
40 countries
Hanefeld, 1990
nateglinide at doses of 30 mg, 60 mg, 120 mg, or 180 mg
versus
placebo
double-blind
Follow-up duration: 12 weeks
Horton, 2000
120 mg nateglinide before meals
versus
placebo
patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in double-blind
Mari, 2005
30, 60, or 120 mg nateglinide
versus
placebo
mild type 2 diabetic men and women (fasting glucose 7.0-8.3 mmol/l) on diet treatment double_blind
Follow-up duration: 24 weeks
Marre, 2002
nateglinide 60 mg, 120 mg before three meals
versus
placebo
metformin-treated patients with HbA1c between 6.8% and 11%double-blind
Moses, 2001
0.5 mg repaglinide at mealtimes (increased to 1 mg after 4 weeks depending on blood glucose response)
versus
placebo
patients with type 2 diabetes considered poorly controlled by diet, but without a history of previous antidiabetic medicationdouble-blind
Follow-up duration: 16 weeks
Saloranta, 2002
nateglinide (30, 60, or 120 mg, with meals).
versus
placebo
patients with type 2 diabetes but only moderately elevated fasting plasma glucose (FPG = 7.0-8.3 mmol/liter)double-blind
Follow-up duration: 24 weeks
nateglinide versus placebo (add on insulin)
Dashora , 2007
nateglinide before meals
versus
placebo
double-blind
Follow-up duration: 16 weeks
nateglinide versus placebo (add on insulin+MET)
Juurinen , 2009
nateglinide (120 mg three times daily) before main meals
versus
placebo (add on insulin+MET)
Type 2 diabetes treated with the combination of basal insulin and metformindouble-blind
Follow-up duration: 24 weeks
nateglinide versus placebo (add on standard treatment)
NCT00402909,
NCT00402909
adding nateglinide to treatment with basal insulin glargine, metformin and/or thiazolidinedione (pioglitazone or rosiglitazone)
versus
patients with type 2 diabetes who are not achieving glycemic control with glargine, metformin and/or thiazolidinedione onlydouble-blind
nateglinide versus repaglinide
Rosenstock , 2004
nateglinide monotherapy
versus
repaglinide monotherapy
type 2 diabetic patients previously treated with diet and exerciseopen
Follow-up duration: 16 week
Li, 2009
Nateglinide
versus
repaglinide
Li, 2007
nateglinide 90 mg three times daily
versus
repaglinide 1.0 mg three times daily
Chinese patients with type 2 diabetes
Follow-up duration: 12 weeks
nateglinide + metformin versus metformin
Horton DOUBLON, 2000
nateglinide (120 mg, ac) and metformin (500 mg, tid)
versus
500 mg metformin three times a day

Follow-up duration: 24 weeks
nifedipine versus ACE inhibitor
JMIC-B (diabetic subgroup), 2004
nifedipine retard
versus
angiotensin converting enzyme inhibitors
outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery diseaseopen
Follow-up duration: 3 years
Japan
nifedipine versus coamilozide
INSIGHT (diabetic subgroup), 2000
Nifedipine GITS 30 mg daily
versus
co-amilozide hydrochlorothiazide 25 mg plus amiloride 2.5 mg
diabetic (subgroup) patients aged 55-80 years with hypertension (blood pressure >= 150/95 mm Hg, or >= 160 mmHg systolic)double-blind
Follow-up duration: 4 y
Europe, Israel
nifedipine versus placebo
ACTION, 1998
Nifedipine GITS
versus
placebo
patients aged at least 35 years with stable angina pectoris and proven coronary artery disease; subgroup of diabetic patientsdouble-blind
Follow-up duration: 4.9y
19 countries
nisoldipine versus enalapril
ABCD (hypertension), 1998
nisoldipine (long acting)
versus
enalapril
patients with non-insulin-dependent diabetes and hypertensionDouble blind
Follow-up duration: 5 y
USA
nitrendipine versus placebo
Syst-Eur (diabetic subgroup), 1999
Calcium-channel blocker
versus
placebo
subgroup of diabetic patients, age, >=60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hgdouble blind
Follow-up duration: 2 years
NPH + GLIM versus lispro mix
Milicevic, 2009
bedtime neutral protamine Hagedorn (NPH) insulin plus maximally tolerated dose of glibenclamide BID
versus
insulin lispro mix 50 pre-breakfast and lispro mix 25 pre-dinner
patients inadequately controlled with oral antihyperglycemic medications open-label
olmesartan versus placebo
ROADMAP, 2010
NCT00185159
olmesartan at 40 mg/day
versus
placebo
patients with diabetes and at least one additional cardiovascular risk factor, but no evidence of renal dysfunctiondouble-blind
Follow-up duration: 3.2 y
Europe (19 countries)
ORIENT,
NCT00141453
olmesartan
versus
placebo
patients with diabetic Nephropathy and overt proteinuria secondary to type 2 diabetes mellitusdouble-blind
Japan, Hong Kong
orlistat versus placebo
Heymsfield, 2000
orlistat 120 mg three times/day
versus
placebo
obese (body mass index, 30-43 kg/m2) adults (WHO 1985 criteria)double blind
Follow-up duration: 4 weeks
USA, Europe
XENDOS (Chiasson), 2002
orlistat 120 mg three times/day
versus
placebo
patients with impaired glucose tolerance (WHO 1994)double blind
Follow-up duration: 3 months
Sweden
perindopril versus placebo
EUROPA (PERSUADE substudy), 2005
perindopril 8mg once daily
versus
placebo
patients with known coronary artery disease and without heart failure, sub group of diabetic patientsdouble-blind
Follow-up duration: 4.3y
PROGRESS (diabetic subgroup), 2001
perindopril 4 mg daily
versus
placebo
hypertensive and non-hypertensive individuals with cerebrovascular disease, subgroup of diatebic patientsdouble-blind
Follow-up duration: 3.9 y
perindopril and indapamide versus placebo
ADVANCE, 2007
NCT00145925
fixed combination of perindopril and indapamide
versus
placebo
patients with type 2 diabetes irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs
ADVANCE, 2007
NCT00145925
low-dose fixed combination of perindopril and indapamide
versus
placebo
individuals with type 2 diabetes double-blind
Follow-up duration: 4.3 yrs
Asia, Australasia, Europe, and North America
picotamide versus placebo
Cocozza, 1995
picotamide 300 mg TID
versus
placebo
normotensive diabetic patients with asymptomatic mild or moderate nonstenotic (< 50%) carotid atherosclerotic lesions and negative history of cerebrovascular ischemic eventsdouble blind
Follow-up duration: 24 months
Italy
pioglitazone versus glimepiride
PERISCOPE, 2008
NCT00225277
pioglitazone 15 to 45 mg
versus
glimepiride, 1 to 4 mg
patients with coronary disease and type 2 diabetesdouble blind
Follow-up duration: 18 months
North and South America
pioglitazone versus metformin
EC404,
Pioglitazone
versus
Metformin
patients with type 2 diabetes
Follow-up duration: 52 wk
pioglitazone versus placebo
PROACTIVE,
NCT00174993
oral pioglitazone titrated from 15 mg to 45 mg
versus
placebo
patients with type 2 diabetes who had evidence of macrovascular disease.
Follow-up duration: 34.5 months
IRIS, 2016
NCT00091949

versus
PNFP-001,
Pioglitazone
versus
Placebo
patients with type 2 diabetes
Follow-up duration: 26 wk
PNFP-012,
Pioglitazone
versus
Placebo
patients with type 2 diabetes
Follow-up duration: 24 wk
PNFP-026,
Pioglitazone
versus
Placebo
patients with type 2 diabetes
Follow-up duration: 16 wk
PROactive, 2005
NCT00174993
pioglitazone titrated from 15 mg to 45 mg
versus
placebo
Inadequately controlled patients with type 2 diabetes who had evidence of macrovascular diseasedouble blind
Follow-up duration: 34.5 mo
19 European countries
pioglitazone versus rosiglitazone
GLAI,
NCT00331487
Pioglitazone
versus
Rosiglitazone
patients with type 2 diabetes and dyslipidemia
Follow-up duration: 24 wk
pioglitazone versus sulfonylurea
EC405,
Pioglitazone
versus
Sulfonylurea
patients with type 2 diabetes
Follow-up duration: 52 wk
OPI-501,
Pioglitazone
versus
Sulfonylurea
Recently diagnosed DM-2
Follow-up duration: 56 wk
OPI-504,
NCT00521820
Pioglitazone
versus
Sulfonylurea
patients with type 2 diabetes andmild to moderate congestive heart failure
Follow-up duration: 24 wk
OPI-506, 0
NCT00494312
Pioglitazone
versus
Sulfonylurea
Inadequately controlled DM-2
Follow-up duration: 156 wk
OPI-520,
NCT00521742
Pioglitazone
versus
Sulfonylurea
Inadequately controlled DM-2 with mild cardiac disease(New York HeartAssociation Class I)
Follow-up duration: 52 wk
pioglitazone versus vildagliptin
Bolli, 2008
vildagliptin (50 mg b.i.d.
versus
pioglitazone (30 mg daily

Follow-up duration: 52 weeks
pioglitazone + insulin versus placebo (add on insulin)
OPI-502,
Pioglitazone + insulin
versus
Placebo + insulin
Insulin-dependent DM-2
Follow-up duration: 20 wk
PNFP-014,
Pioglitazone insulin
versus
Placebo + insulin
patients with type 2 diabetes
Follow-up duration: 16 wk
pioglitazone + metformin versus placebo (add on MET)
PNFP-027,
Pioglitazone + metforminrea
versus
Placebo +metformin
patients with type 2 diabetes
Follow-up duration: 16 wk
pioglitazone + metformin versus sulfonylurea + metformin
EC410,
Pioglitazone + metformin
versus
Sulfonylurea + metformin
patients with type 2 diabetes
Follow-up duration: 104 wk
pioglitazone + sulfonylurea versus metformin + sulfonylurea
EC409,
Pioglitazone + sulfonylurea
versus
Metformin + sulfonylurea
patients with type 2 diabetes
Follow-up duration: 104 wk
pioglitazone + sulfonylurea versus sulfonylurea
PNFP-010,
Pioglitazone + sulfonylurea
versus
Sulfonylurea
patients with type 2 diabetes
Follow-up duration: 16 wk
prandial plus basal versus basal insulin
Hirsch A VOIR (MA), 0
insulin lispro protamine suspension plus insulin lispro
versus
basal insulin glargine
metformin-treated patients with type 2 diabetes
prandial premixed therapy versus basal/bolus therapy
Garber, 2006
prandial premixed therapy
versus
basal/bolus therapy
prandial premixed therapy tid versus basal/bolus therapy
Rosenstock, 2008
lispro mix 50/50: 50% insulin lispro protamine suspension and 50% lispro 3 times daily (prandial premixed therapy)
versus
glargine at bedtime plus mealtime lispro (basal/bolus therapy)
pravastatin versus placebo
PROSPER (sub group), 2002
pravastatin 40mg daily
versus
placebo
mena and women aged 70–82 years with a history of, or risk factors for, vascular diseasedouble blind
Follow-up duration: 3.2y mean
LIPID (sub group), 1998
pravastatin 40 mg daily
versus
placebo
patients with a history of myocardial infarction or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliterdouble blind
Follow-up duration: mean 6.1y
Australia, New Zealand
CARE (sub group), 1998
pravastatin
versus
placebo
men and postmenopausal women between 21 to 75 years of age, with MI between 3 and 20 months before randomization and plasma total cholesterol values <240mg/dL, LDL-C levels between 115 and 174mg/dL, and triglycerides <350mg/dL
WOSCOPS (sub group), 1996
pravastatin 40 mg daily
versus
placebo
men aged 45-64 years with no history of myocardial infarction and plasma total cholesterol concentrations of 6.5-8.0 mmol/L at initial screeningdouble blind
Follow-up duration: mean 4.9y
pravastatin versus usual care
GISSI P (sub group), 2000
pravastatin 20 mg daily
versus
usual care
recent acute myocardial infarction patients (< or = 6 months) with total blood cholesterol > or = 200 mg/dl open
Follow-up duration: median 24.3 months
ALLHAT-LLT (sub group), 2002
pravastatin
versus
usual care
Ambulatory persons aged 55 years or older, with lowdensity lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dLopen
pravastatin high dose versus pravastatin
PROVE IT TIMI 22 (diabetic sub group), 2006
pravastatin 80mg daily
versus
pravastatin 40mg daily
patients hospitalized for an acute coronary syndrome within the preceding 10 daysdouble blind
Follow-up duration: 24 months mean
premix aspart70/30 twice daily versus once daily insulin glargine
INITIATE (Raskin) DOUBLON, 2008
biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper)
versus
once-daily insulin glargine
insulin-naive patients with HbA1c values 8.0% on 1,000 mg/day metformin alone or in combination with other OADs
premix lispro 50/50 thrice time versus glargine once daily
Robbins, 2007
NCT00191464)
lispro mix 50/50 (50% insulin lispro protamine suspension [ILPS] and 50% lispro) TID for 24 weeks
versus
insulin glargine QD at bedtime
patients with type 2 diabetes mellitus and an HbA(1c) level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injectionsopen-label
Follow-up duration: 24 weeks
Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States
Kazda, 2006
3x daily lispro mid mixture (MidMix; 50% lispro, 50% protaminated lispro),
versus
1x daily insulin glargine
patients with type 2 diabetes starting insulin treatmentopen-label
Follow-up duration: 24 week
Germany
premix lispro 75/25 twice daily versus glargine once daily
DURABLE (Buse) DOUBLONS, 2011
lispro mix 75/25 twice daily
versus
once-daily insulin glargine
type 2 diabetes patients
DURABLE (Buse), 2009
NCT00279201
twice-daily lispro mix 75/25
versus
daily glargine
patients with type 2 diabetes mellitus failing to achieve control with starter insulin treatment and continuing oral antihyperglycemic drugs
Follow-up duration: 24 weeks
Malone, 2004
mixture of 75% insulin lispro protamine suspensionand 25% insulin lispro (Mix 75/25) BID
versus
insulin glargine QD
patients with type 2 diabetes beginning insulin therapyopen-label
Follow-up duration: 16 week
USA
Malone, 2005
insulin lispro mixture (25%insulin lispro and 75% NPL) twice daily
versus
once-daily insulin glargine
patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy
Follow-up duration: 32 weeks
premix lispro thrice daily versus glargine once daily
Jacober, 2006
intensive insulin lispro mixture therapy for 4 months
versus
once-daily insulin glargine
insulin-naïve patients with type 2 diabetes receiving oral antidiabetes agents
Follow-up duration: 4 months
premixed insulin lispro versus basal-bolus
Masuda, 2008
twice-daily 50/50 premixed insulin lispro
versus
NPH insulin at bedtime and preprandial insulin lispro
insulin-naïve type 2 diabetic patients
ramipril versus placebo
DREAM ramipril, 2006
NCT00095654
ramipril up to 15 mg daily
versus
placebo
patients with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular diseasedouble blind
Follow-up duration: 3 y (median)
21 countries
DIABHYCAR, 2004
ramipril 1.25 mg/day
versus
placebo
patients with type 2 diabetes who have microalbuminuria or proteinuriadouble-blind
Follow-up duration: median 4 years
Europe, North Africa
DREAM, 2008
ramipril(up to 15 mg per day)
versus
placebo
people aged >=30 years, with Impaired glucose tolerance and/or impaired fasting glucose without known CVD or renal insufficiencyopen
Follow-up duration: 3 years
repaglinide versus ???
YSRE0001, 0
NCT00336310
Repaglinide
versus
NA
double-blind
Follow-up duration: 12 weeks
Taiwan
repaglinide versus control (add on MET)
Moses, 1999
prestudy dose of metformin with the addition of repaglinide
versus
prestudy dose of metformin
patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin open
Follow-up duration: 12 weeks
repaglinide versus glibenclamide
Landgraf, 1999
repaglinide, administered preprandially three times daily
versus
glibenclamide, given preprandially once or twice daily
double-blind
Follow-up duration: 14 weeks
Marbury, 1999

versus
Wolffenbuttel, 1999
repaglinide (0.5-4 mg t.i.d.)
versus
glyburide (1.75-10.5 mg daily)
double-blind
Follow-up duration: 1 year
repaglinide versus gliclazide
AGEE-3783, 0
NCT01022762
repaglinide (1 mg repaglinide twice daily (weeks 0-4), titrated
versus
gliclazide (80 mg gliclazide once daily (weeks 0-4), titrated
Chinese subjects with type 2 diabetes who never have been treated with oral anti-diabetic drugs
China
repaglinide versus glipizide
Madsbad, 2001
repaglinide, 1-4 mg at mealtimes
versus
glipizide, 5-15 mg daily
double-blind
Follow-up duration: 1 year
repaglinide versus Metformin
ReMet, 0
NCT00118950
Repaglinide
versus
Metformin
Non-Obese Type 2 Diabetic Patients Uncontrolled by Dietdouble-blind
Denmark
repaglinide versus metformin
Lund, 2007
repaglinide 2 mg thrice daily
versus
metformin 1 g twice daily
non-obese patients with type 2 diabetesdouble-blind
repaglinide versus Metformin (add on insulin)
Reform, 0
NCT00118963
Repaglinide + BIAsp30
versus
Metformin + BIAsp30
non-obese patients with type-2-diabetes, uncontrolled on diet alonedouble-blind
repaglinide versus on top pioglitazone
Raskin, 2001

versus
repaglinide versus on top rosiglitazone
Raskin, 2001

versus
repaglinide versus on top troglitazone
Raskin, 2000
repaglinide (0.5–4.0 mg at meals),
versus
combination of repaglinide (1–4 mg at meals) and troglitazone (200–600 mg once daily)
Patients with type 2 diabetes who had inadequate glycemic control (HbA1c 7.0%) during previous monotherapyopen
Follow-up duration: 22 weeks
repaglinide versus placebo
Goldberg, 1998
repaglinide
versus
placebo
patients with type 2 diabetesdouble-blind
Follow-up duration: 18 weeks
Jovanovic, 2000
repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146)
versus
placebo
double-blind
Follow-up duration: 24 weeks
Chuang, 1999

versus
Bech, 2003
repaglinide initiated at 0.5 mg per meal, increased to 1 mg after 4 weeks if fasting plasma glucose exceeded 7.8 mmol/l.
versus
placebo
pharmacotherapy-naive patients with Type 2 diabetesdouble-blind
Follow-up duration: 16 weeks
Goldberg, 1998
repaglinide
versus
placebo
type 2 diabetesdouble-blind
Jovanovic, 2000
repaglinide 1 mg or repaglinide 4 mg
versus
placebo
double-blind
Follow-up duration: 24 weeks
repaglinide versus placebo (on top bedtime NPH-insulin)
Landin-Olsson, 1999

versus
repaglinide + insulin versus insulin
AGEE-1524, 0
NCT00799448
repaglinide combined with insulin NPH
versus
biphasic human insulin 30 alone
type 2 diabetics inadequately controlled with sulfonylurea (SU) +/ biguanide therapy open
Greece
AGEE-3020,

versus
repaglinide + metformin versus metformin
AGEE-1411,
NCT01465152
metformin and repaglinide
versus
open
Spain
repaglinide + metformin versus repaglinide
AGEE-3705, 0
NCT00819741
repaglinide plus metformin
versus
repaglinide alone
Chinese subjects with type 2 diabetes having an HbA1c (glycosylated haemoglobin A1c) over 8.5 % and who never have taken oral sugar-lowering drugs beforeopen
China
AGEE-3018,

versus
repaglinide + metformin versus rosiglitazone + metformin
Raskin , 2009
NCT00399711
repaglinide and metformin fixed dose combination tablet given as twice daily
versus
twice daily rosiglitazone and metformin fixed dose combination
subjects with type 2 diabetes currently on monotherapyopen
Follow-up duration: 26 weeks
USA
repaglinide + metformin versus SU or MET
AGEE-3017, 0
NCT00568984
combination therapy of repaglinide and metformin
versus
conventional treatment with a sulphonylurea or metformin in monotherapy

China
rosiglitazone versus control
Wang, 2005
rosiglitazone 4 mg/d
versus
control
patients with diabetes and CAD who had undergone percutaneous coronary interventionopen
Follow-up duration: 6 months
rosiglitazone versus glipizide
APPROACH, 2008
NCT00116831
rosiglitazone at up to 8 mg/day
versus
glipizide at 15 mg/day
patients with type 2 diabetes and coronary artery diseasedouble blind
Follow-up duration: 18 months
rosiglitazone versus glyburide
49653/020 ,
Rosiglitazone
versus
Glyburide
patients with type 2 diabetes
Follow-up duration: 52 wk
49653/079 ,
Rosiglitazone with or without glyburide
versus
Glyburide
patients with type 2 diabetes poorly controlled on maximum dose of Gly
Follow-up duration: 26 wk
49653/080 ,
Rosiglitazone
versus
Glyburide
patients with type 2 diabetes
Follow-up duration: 156 wk
49653/097 ,
Rosiglitazone
versus
Glyburide
patients with type 2 diabetesDM
Follow-up duration: 156 wk
49653/143 ,
NCT00333723
Rosiglitazone and glyburide
versus
Glyburide
Type 2 DM poorly controlled on glyburide
Follow-up duration: 24 wk
rosiglitazone versus glyburide (add on MET)
49653/137 ,
NCT00500955
Rosiglitazone and metformin
versus
Glyburide and metformin
patients with type 2 diabetes
Follow-up duration: 32 wk
rosiglitazone versus metformin
49653/093 ,
Rosiglitazone with or without metformin
versus
Metformin
patients with type 2 diabetes poorly controlled on Met
Follow-up duration: 26 wk
49653/094 ,
Rosiglitazone and metformin
versus
Metformin
Type 2 DM poorly controlled on Met
Follow-up duration: 26 wk
rosiglitazone versus metformin/sulfonylurea
RECORD, 2013
NCT00379769

versus
rosiglitazone versus placebo
49653/011 ,
Rosiglitazone
versus
Placebo
patients with type 2 diabetes
Follow-up duration: 24 wk
DREAM rosiglitazone, 2006
NCT00095654
rosiglitazone 8 mg daily
versus
placebo
patients with impaired fasting glucose or impaired glucose tolerance, or bothdouble blind
Follow-up duration: 3 years (median)
21 countries
49653/128 ,
Rosiglitazone
versus
Placebo
patients with type 2 diabetes on concurrent Su
Follow-up duration: 28 wk
49653/134 ,
Rosiglitazone
versus
Placebo
patients with type 2 diabetes on Gly and Met
Follow-up duration: 28 wk
49653/136 ,
Rosiglitazone
versus
Placebo
patients with type 2 diabetes and chronic renal failure on Su, insulin, or both
Follow-up duration: 26 wk
49653/330 ,
Rosiglitazone
versus
Placebo
Chronic psoriasis
Follow-up duration: 52 wk
49653/331 ,
Rosiglitazone
versus
Placebo
Chronic psoriasis
Follow-up duration: 52 wk
AVA100193 ,
Rosiglitazone
versus
Placebo
Mild-to-moderate Alzheimer’s disease
Follow-up duration: 24 wk
BRL 49653/334 ,
NCT00306644
Rosiglitazone
versus
Placebo
patients with type 2 diabetes or insulin resistance syndrome
Follow-up duration: 52 wk
rosiglitazone versus placebo (add on glicazide)
49653/145 ,
Rosiglitazone and gliclazide
versus
Gliclazide
patients with type 2 diabetes
Follow-up duration: 26 wk
rosiglitazone versus placebo (add on glimepiride)
49653/234 ,
Rosiglitazone and glimepiride
versus
Glimepiride
patients with type 2 diabetes
Follow-up duration: 26 wk
rosiglitazone versus placebo (add on glipizide)
49653/135 ,
Rosiglitazone and glipizide
versus
Glipizide
Elderly patients with type 2 DM
Follow-up duration: 104 wk
rosiglitazone versus placebo (add on glyburide)
100684 ,
NCT01045590
Rosiglitazone and glyburide
versus
Glyburide
Korean patients with type 2 DM
Follow-up duration: 52 wk
49653/127 ,
Rosiglitazone and glyburide
versus
Glyburide
patients with type 2 diabetespoorly controlled on Gly
Follow-up duration: 26 wk
49653/162 ,
Rosiglitazone and glyburide
versus
Glyburide
patients with type 2 diabetes
Follow-up duration: 26 wk
rosiglitazone versus placebo (add on insulin)
49653/085 ,
Rosiglitazone and insulin
versus
Insulin
patients with type 2 diabetes
Follow-up duration: 26 wk
49653/095 ,
Rosiglitazone and insulin
versus
Insulin
patients with type 2 diabetes poorly controlled on insulin
Follow-up duration: 26 wk
BRL 49653/347 ,
NCT00054782
Rosiglitazone and insulin
versus
Insulin
patients with type 2 diabetes poorly controlled on insulin
Follow-up duration: 24 wk
rosiglitazone versus placebo (add on MET)
49653/284 ,
NCT00501020
Rosiglitazone and metformin
versus
Metformin
patients with type 2 diabetes
Follow-up duration: 24 wk
712753/008 ,
NCT00241605
Rosiglitazone and metformin
versus
Metformin
Type 2 DM poorly controlled on Met
Follow-up duration: 48 wk
SB-712753/002 ,
Rosiglitazone and metformin
versus
Metformin
patients with type 2 diabetes poorly controlled
Follow-up duration: 24 wk
SB-712753/003 ,
Rosiglitazone and metformin
versus
Metformin
Mild type 2 DM
Follow-up duration: 32 wk
rosiglitazone versus placebo (add on SU)
49653/015 ,
Rosiglitazone and sulfonylurea
versus
Sulfonylurea
patients with type 2 diabetes
Follow-up duration: 24 wk
49653/125 ,
NCT00422955
Rosiglitazone and sulfonylurea
versus
Sulfonylurea
patients with type 2 diabetes
Follow-up duration: 26 wk
49653/132 ,
Rosiglitazone and sulfonylurea
versus
Sulfonylurea
Patients in China with type 2 DM
Follow-up duration: 24 wk
49653/147 ,
Rosiglitazone and sufonylurea
versus
Sulfonylurea
Indo-Asian patients with type 2 diabetes
Follow-up duration: 26 wk
rosiglitazone versus standard glucose-lowering drugs
ADOPT, 2006
NCT00279045
Rosiglitazone 4mg twice daily
versus
Metformin 1000mg twice daily or glyburide 7.5mg twice daily
Recently diagnosed type type 2 diabetesdouble blind
Follow-up duration: 4y (median)
United States, Canada, Europe
RECORD, 2009
NCT00379769
addition of rosiglitazone (4-8 mg daily titrated) to metformin or sulfonylurea, target HbA1c<=7·0%
versus
combination of metformin and sulfonylurea, target HbA1c<=7·0%
patients with type 2 diabetes onmonotherapy with either metformin or sulfonylurea andin less than optimal blood glucose control (HbA1c >7·0–9·0%)open
Follow-up duration: 5.5 y
Europe, Australia
rosiglitazone versus usual care
49653/211 ,
Rosiglitazone and usual care
versus
Usual care
Type 2 DM with CHF
Follow-up duration: 52 wk
rosiglitazone and metformin versus placebo
CANOE, 2010
NCT00116932
rosiglitazone (2 mg) and metformin (500 mg) twice-daily
versus
placebo
patients with impaired glucose tolerance double-blind
Follow-up duration: 3.9y (median)
saxagliptin versus glipizide
saxagliptin,
saxagliptin
versus
titrated glipizide plus metformin
adult patients with type 2 diabetes and inadequate glycemic controldouble-blind
Follow-up duration: 52 weeks
saxagliptin versus placebo
SAVOR TIMI, 2013
NCT01107886
saxagliptin
versus
placebo
patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular eventsdouble-blind
Follow-up duration: 2.1 years (median)
SAVOR-TIMI 53, 2013
NCT01107886
Saxagliptin 5 mg or 2.5 mg once daily
versus
Placebo
Patients With Type 2 Diabetes
USA
saxagliptin versus placebo (add on current treatment)
saxgliptin, renal study,
saxagliptin
versus
placebo added to patients’ current diabetes treatment
patients with moderate to severe renal impairment or end-stage renal disease
Follow-up duration: 12 weeks
saxagliptin versus placebo (add on insulin)
CV181-057,
NCT00757588
Saxagliptin, 5 mg
versus
placebo (on top insulin)
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin
saxagliptin versus placebo (add on MET)
CV181-066,
NCT00683657
Saxagliptin
versus
placebo
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet And Exercise And A Stable Dose Of Metformin ¡Ý1500 mg/Day
CV181-080,
NCT00885378
2.5 mg Saxagliptin, Twice Daily
versus
placebo
Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone
DeFronzo, 2009
NCT00121667
saxagliptin (2.5, 5, or 10 mg once daily)
versus
placebo
Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone
Follow-up duration: 24 weeks
Jadzinsky, 2009
NCT00327015
saxagliptin
versus
placebo
treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control
saxagliptin versus placebo (add on TZD)
Hollander,
NCT00295633
saxagliptin (2.5 or 5 mg)
versus
placebo
patients with type 2 diabetes and inadequate control on thiazolidinedione alone
saxagliptin versus placebo (monotherapy)
CV181-011,
NCT00121641
oral saxagliptin 2.5, 5, or 10 mg once daily
versus
placebo

Follow-up duration: 24 weeks
CV181-038,
NCT00316082
Saxagliptin monotherapy
versus
placebo
type 2 diabetic subjects who are not controlled with diet and exercise
CV181-041,
NCT00374907
Saxagliptin
versus
placebo
Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise
Rosenstock, 2008
NCT00950599
saxagliptin 2.5, 5, 10, 20 or 40 mg once daily
versus
placebo
drug-naive patients with T2DM and inadequate glycaemic control
Follow-up duration: 12 weeks
saxagliptin versus sitagliptin (add on MET)
saxagliptin vs sitagliptin,
saxagliptin 5 mg once daily add on metformin
versus
sitagliptin 100 mg onece daily add on metformin
adults with type 2 diabetes who did not attain adequate glycemic control on metformin therapy alone
Follow-up duration: 18 weeks
saxagliptin + glyburide versus glyburide uptitration
CV181-040,
NCT00313313
saxagliptin added to a submaximal sulphonylurea dose
versus
uptitration of sulphonylurea monotherapy
patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy
Follow-up duration: 24 weeks
saxagliptin plus metformin XR 1500mg versus metformin up to 2000mg
CV181-085,
NCT00918138
Saxagliptin in Combination With Metformin XR 1500 mg
versus
Up-titrated Metformin XR to 2000 mg
Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise and a Stable Dose of Metformin XR 1500 mg
screening for CAD versus no screening
DIAD, 2009
NCT00769275
screening with adenosine-stress radionuclide myocardial perfusion imaging (MPI)
versus
no screening
participants with type 2 diabetes and no symptoms of CADopen
Follow-up duration: 4.8 years
USA, Canada
DYNAMIT, 2010
NCT00627783
screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography
versus
no screening
diabetic patients with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors open
France
semaglutide versus placebo
SUSTAIN 6, 2016
NCT01720446
once-weekly semaglutide (0.5 mg or 1.0 mg)
versus
placebo
patients with type 2 diabetes who were on a standardcare regimendouble-blind
Follow-up duration: 2.1 y (median)
20 countries
simvastatin versus placebo
HPS (sub group), 2002
simvastatin 40mg daily
versus
placebo
Men and women diabetes aged about 40–80 years with non-fasting blood total cholesterol concentrations of at least 3·5 mmol/L (135 mg/dL)double blind
4S (sub group), 1999
simvastatin
versus
placebo
diabetic men and women aged 35 to 70 years with previous MI or active, stable angina pectoris and with serum total cholesterol level between 5.5 to 8.0 mmol/L and serum triglyceride level <=2.5 mmol/Ldouble blind
Follow-up duration: 5.4y
Denmark, Finland, Iceland, Norway, and Sweden
sitagliptin versus control (add on MET)
Reasner, 2011
NCT00482729)
sitagliptin/metformin 50/500 mg bid uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid
versus
metformin monotherapy
drug-naive patients with type 2 diabetesNA
sitagliptin versus glimepiride (add on MET)
Arechavaleta, 2011
NCT00701090
sitagliptin 100 mg daily
versus
glimepiride (starting dose 1 mg/day and up-titrated, based upon patient's self-monitoring of blood glucose results, to a maximum dose of up to 6 mg/day)
patients with type 2 diabetes inadequately controlled on metformin monotherapydouble-blind
Follow-up duration: 30 weeks
sitagliptin versus metformin
Goldstein (sit vs met), 2007
sitagliptin 100 dailyily
versus
metformin 1000 mg or 2000 mg daily;imag
Goldstein (sit+met vs met), 2007
sitagliptin 50 mg daily plus metformin 1000 or 2000 mg dailyç$4
versus
metformin 1000 or 2000 mg daily
sitagliptin versus pioglitazone
Pérez-Monteverde, 2011
NCT00541450
sitagliptin100 mg qd
versus
pioglitazone 15 mg qd, up-titrated to 30 mg after 6 weeks
drug-naïve patients with type 2 diabetesdouble-blind
Follow-up duration: 12 weeks
sitagliptin versus placebo
Goldstein, 2007
NCT00103857
sitagliptin 100 mg daily
versus
placebo
Hanefeld, 2007
sitagliptin 25 mg or 50 mg or 100 mg dailyi
versus
placebo
TECOS, 2015
NCT00790205
sitagliptin phosphate, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily
versus
placebo
patients with Type 2 Diabetes Mellitus having a history of cardiovascular disease and a hemoglobin A1c (HbA1c) of 6.5% to 8.0%double-blind
Follow-up duration: 3.0 years (median)
38 countries
sitagliptin versus placebo (add on insulin+/-MET)
Vilsbøll, 2010
NCT00395343
once-daily sitagliptin 100 mg
versus
placebo
patients with type 2 diabetes inadequately controlled on long-acting, intermediate-acting or premixed insulin double-blind
sitagliptin versus placebo (add on MET)
Charbonnel, 2006
NCT0086515
sitagliptin 100 mg daily (add-on to metformin therapy)j
versus
placebo (add-on tometformin therapy);
Nauck, 2007
NCT00094770
sitagliptin 100 mg daily (add-on to metformin therapy)j
versus
placebo (add-on to metformin therapy);
raz, 2008
NCT00337610
sitagliptin 100 mg once daily
versus
placebo
patients with type 2 diabetes
Scott** (sit vs pbo on top met), 2007
sitagliptin 100 mg daily (add-on to metformin therapy)j
versus
placebo (add-on to metformin therapy).
patients with type 2 diabetes who were inadequately on mET monotherapy
sitagliptin versus placebo (add on PIO)
Rosenstock , 2006
NCT00086502
sitagliptin 100 mg once daily
versus
placebo
patients with type 2 diabetes and inadequate glycemic control double-blind
Follow-up duration: 24 weeks
sitagliptin versus placebo (on top PIO)
Rosenstock (sit on top pio vs pbo), 2006
NCT00086502
sitagliptin 100 mg daily (add-on to pioglitazone therapy)sl˜ðõØ
versus
placebo (add-on to pioglitazone therapy);
sitagliptin versus placebo (on-top glimepiride+/- metformine)
Hermansen, 2007
sitagliptin 100 mg daily (add-on to ongoing stable doses of glimepiride, alone or in combination with metformin)ocumen
versus
placebo (add-on to ongoing stable doses of glimepiride, alone or in combination with metformin);
sitagliptin versus rosiglitazone (add on MET)
Rigby , 2010
sitagliptin phosphate, 100 mg daily
versus
rosiglitazone maleate, 4 mg daily
type 2 diabetes mellitus inadequately controlled by metformin monotherapyopen
Follow-up duration: 16 weeks
sitagliptin versus Sulphonylurea (on top MET)
Al Sifri, 2011
sitagliptin 100 mg qd
versus
prestudy sulphonylurea
Muslim patients with type 2 diabetes who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months open
sitagliptin 50mg bid monotherapy versus glipizide
Scott* (sit vs glipi), 2007
sitagliptin 50mg bid
versus
glipizide 5mg to 20 mg dailyitm
patients with type 2 diabetes who have inadequate glycaemic control on diet and exercisedouble-blind
Follow-up duration: 12 weeks
sitagliptin 50mg bid monotherapy versus placebo
Scott* (sit vs pbo), 2007
sitagliptin 50 mg b.i.d
versus
placebo
sitagliptin monotherapy versus metformin
Aschner, 2010
NCT00449930
once-daily sitagliptin 100 mg
versus
twice-daily metformin 1000 mg
treatment-naïve patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
sitagliptin monotherapy versus placebo
Aschner, 2006
NCT00087516
sitagliptin 100 or 200 mg dailym
versus
placebo
patients with type 2 diabetes
Follow-up duration: 24 weeks
Barzilai, 2011
NCT00305604
once-daily sitagliptin (100 or 50 mg, depending on renal function)
versus
placebo
elderly patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
US
Chan, 2008
sitagliptin
versus
placebo
patients with type 2 diabetes and chronic renal insufficiencydouble-blind
Follow-up duration: 12 weeks
Mohan , 2009
sitagliptin 100mg once daily monotherapy
versus
placebo
Chinese, Indian, and Korean patients with type 2 diabetes inadequately controlled by diet and exercise.double-blind
Follow-up duration: 18 weeks
Nonaka, 2008
NCT00371007
sitagliptin 100 mg daily monotherapy
versus
placebo
Japanese patients with type 2 diabetesdouble-blind
Raz, 2006
sitagliptin 100 mg (or 200 mg) daily
versus
placebo
patients with type 2 diabetes mellitus and inadequate glycaemic control
sitagliptin monotherapy versus voglibose
Iwamoto , 2010
sitagliptin 50 mg once daily monotherapy
versus
voglibose 0.2 mg thrice daily before meals
Japanese patients with type 2 diabetesdouble-blind
Follow-up duration: 12 weeks
sitagliptin+pio versus metformin+pio
Derosa , 2010
pioglitazone 30 mg plus sitagliptin 100 mg once a day
versus
pioglitazone 15 mg plus metformin 850 mg twice a day
poorly controlled type 2 diabetes mellitus patients
SU versus rosiglitazone (add on MET)
Hamann, 2008
combination sulphonylurea plus metformin
versus
rosiglitazone/metformin fixed-dose combination
overweight individuals with inadequately controlled type 2 diabetes mellitus.Individuals with inadequate glycaemic control (HbA (1c)> or =7%) while on metformin monotherapy (> or =0.85 g/day)
Follow-up duration: 52 weeks
sulfinyrazone versus placebo
Dutch, 1980
sulfinyrazone
versus

Follow-up duration: 32 months
taspoglutide versus placebo (add on MET)
Ratner (20mg once weekly), 2010
NCT00460941
taspoglutide s.c. 20mg once weekly for 8 weeks
versus
placebo s.c. once weekly on top metformin
subjects with Type 2 diabetes inadequately controlled on metformin alonedouble-blind
Follow-up duration: 8 weeks (+4wk)
Australia, France, Germany, Mexico, Peru, USA
taspoglutide 10mg once weekly versus placebo
Nauck 10 once weekly vs PBO, 2009
NCT00423501
taspoglutide, either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks for 8 weeks
versus
placebo
patients with type 2 diabetes inadequately controlled with metformindouble-blind
Follow-up duration: 12 weeks
taspoglutide 20mg once every 2 weeks versus placebo
Nauck 20 every 2 weeks vs PBO, 2009

versus
taspoglutide 20mg once weekly versus placebo
Nauck 20 once weekly vs PBO, 2009

versus
telmisartan versus placebo
PROFESS, 2008
80 mg telmisartan once daily
versus
placebo
double-blind
Follow-up duration: 2.4y
temisartan versus enalapril
DETAIL, 2004
telmisartan 80 mg daily
versus
enalapril 20 mg daily
subjects with type 2 diabetes and early nephropathydouble-blind
Follow-up duration: 5 years
northern Europe
ticlopidine versus placebo
Birmingham-A, 1979
ticlopidine 100, 250, 500 mg
versus

Follow-up duration: 2 months
London diabetes, 1983
ticlopidine 500mg
versus

Follow-up duration: 12 months
TIMAD, 1984
ticlopidine 500mg
versus

Follow-up duration: 32m
BTRS, 1992
ticlopidine 500mg/d
versus
placebo
insulin-treated diabetics with background retinopathydouble blind
Follow-up duration: 48 months
Nyberg, 1984
ticlopidine 500mg daily
versus
placebo
insulin dependent diabetes complicated by nephropathydouble blind
Follow-up duration: 12 months
tolbutamide or phenformin versus placebo
UGDP (Tolb or Phen), 1975
tolbutamide(1.5mg daily) or phenformin (100mg daily)
versus
placebo
patient with non insulin-dependent adult onset diabetes double-blind
Follow-up duration: >5 years
troglitazone versus placebo
TRIPOD (Buchanan), 2002
troglitazone 400 mg once daily
versus
placebo
Hispanic women with previous gestational diabetesdouble blind
Follow-up duration: 30 months (median)
USA
US DDP troglitazone (Knowler), 2005
troglitazone
versus
double placebo
nondiabetic patients with elevated glucose and high risk for diabetesdouble blind
Follow-up duration: 0.9 year
USA
valsartan versus amlodipine
NAGOYA HEART, 2011
NCT00129233
blood-pressure-lowering therapy based on valsartan; blood-pressure goal of <130/80 mm Hg
versus
blood-pressure-lowering therapy based on amlodipine; blood-pressure goal of <130/80 mm Hg
patients with hypertension with type 2 diabetes or impaired glucose toleranceopen
Follow-up duration: 3.2 y median
Japan
valsartan versus placebo
NAVIGATOR valsartan, 2010
NCT00097786
valsartan up to 160 mg daily
versus
placebo
subjects with impaired glucose tolerance and either CV disease or CV risk factorsdouble-blind
Follow-up duration: 5 years
40 countries
verapamil versus control
INVEST (subgroup), 2003
calcium antagonist strategy (verapamil sustained release)
versus
non-calcium antagonist strategy (atenolol)
hypertensive CAD patients aged 50 years or olderopen
Follow-up duration: 24 months
14 countries
vildagliptin versus gliclazide (add on MET)
Filozof, 2009
NCT00102466
vildagliptin (50 mg twice daily
versus
gliclazide (up to 320 mg/day
patients with Type 2 diabetes inadequately controlled with metformin double-blind
Follow-up duration: 52 weeks
vildagliptin versus glimepiride (add on MET)
Matthews , 2010
vildagliptin
versus
glimepiride
patients with type 2 diabetes mellitus inadequately controlled (HbA1c 6.5-8.5%) by metformin monotherapydouble-blind
Follow-up duration: 2 years
vildagliptin versus metformin
Goke, 2008
vildagliptin (100 mg daily)
versus
metformin (2 000 mg daily).
drug-naïve patients with type 2 diabetes
Schweizer, 2007
NCT00099866
vildagliptin 100mg
versus
metformin up to 2000 mg daily
drug-naïve patients with Type 2 diabetes
Follow-up duration: 52 weeks
Schweizer, 2009
NCT00246619
vildagliptin (100 mg daily
versus
metformin (titrated to 1500 mg daily
drug-naïve patients with type 2 diabetes aged>or=65 years
vildagliptin versus pioglitazone (add on MET)
Bolli, 2008
NCT00237237
vildagliptin 100 mg daily (add-on to metformin therapy)
versus
pioglitazone 30 mg daily (add-on to metformin therapy)j
patients with type 2 diabetes inadequately controlled with metformin monotherapydouble-blind
vildagliptin versus placebo
Mimori, 2006
vildagliptin 20 mg or 50 mg or 100 mg daily
versus
placebo
NCT00351832,
NCT00351832
vildagliptin 50mg qd, 50mg bid or 100mg qd
versus
placebo
Patients With Type 2 Diabetes
Follow-up duration: 12 weeks
Japan
Rosenstock, 2008
NCT00237250
vildagliptin (50 mg q.d.)
versus
placebo
subjects with impaired glucose tolerance double-blind
Follow-up duration: 12 weeks
Scherbaum [2], 2008
NCT00101712
vildagliptin 50 mg qd
versus
placebo
drug-naïve patients with type 2 diabetes and mild hyperglycaemiadouble-blind
Follow-up duration: 52 weeks
vildagliptin versus placebo (add on current therapy)
Lukashevich , 2011
NA
vildagliptin (50 mg qd)
versus
placebo
patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment
Follow-up duration: 24 weeks
vildagliptin versus placebo (add on glimepiride)
Kikuchi, 2010
NCT00325117
vildagliptin 50mg twice-daily
versus
placebo
Japanese patients with Type 2 diabetes mellitusdouble-blind
Follow-up duration: 12 weeks
Japan
vildagliptin versus placebo (add on insulin)
Fonseca, 2007
NCT00099931
vildagliptin 100 mg daily (add-on to insulin therapy)y)
versus
placebo (add-on to insulin therapy)y)mag
type 2 diabetes that was inadequately controlled by insulindouble-blind
Follow-up duration: 24 weeks
Fonseca , 2008
vildagliptin added to insulin
versus
vildagliptin versus placebo (add on MET)
Ahren, 2004
vildagliptin 50 mg daily (add-on to metformin therapy)j
versus
placebo (add-on to metformin therapy)mag
patients with type 2 diabetes double-blind
Follow-up duration: 12 weeks
Bosi, 2007
NCT00099892
vildagliptin (50 or) 100 mg daily (add-on to metformin therapy)m
versus
placebo (add-on to metformin therapy)mag
patients with type 2 diabetes inadequately controlled with metformindouble-blind
Bosi, 2009
NCT00382096
vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily),
versus
high-dose metformin monotherapy (1000 mg twice daily).
treatment-naive patients with type 2 diabetes mellitus
Follow-up duration: 24 weeks
Goodman, 2009
ildagliptin 100 mg given in the morning, vildagliptin 100 mg given in the evening
versus
placebo
patients inadequately controlled with metformindouble-blind
Follow-up duration: 24 weeks
NCT00396071,
NCT00396071
vildagliptin
versus
placebo
Patients With Type 2 Diabetes Treated With Metformin
NCT00494884 (Wollmer),
NCT00494884
Vildagliptin 100 mg o.d.
versus
placebo
Patients With Type 2 Diabetes Inadequately Controlled With Metformin
NCT00728351,
NCT00728351
Vildagliptin and Metformin (25/1000 mg Bid)
versus
Metformin Monotherapy (1000 mg Bid)
Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
NCT00822211,
NCT00822211
Vildagliptin 50 mg Bid or qd
versus
placebo
Chinese Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
Follow-up duration: 24 weeks
vildagliptin versus placebo (add on SU)
Garber, 2008
NCT00099944
vildagliptin (50 mg given once or twice daily)
versus
placebo
patients with type 2 diabetes inadequately controlled with a sulphonylureadouble-blind
Follow-up duration: 24 weeks
vildagliptin versus placebo (add on TZD)
Rosenstock** (vilda + pio vs pio), 2007
NCT00101803
vildagliptin 50 mg or 100 mg daily plus 15 mg or 30 mg pioglitazone dailyi
versus
pioglitazone 30 mg daily
drug-naive patients with type 2 diabetes double-blind
Follow-up duration: 24 weeks
vildagliptin versus placebo (on top pioglitazone)
Garber, 2007
NCT00099853
vildagliptin 50 or 100 mg daily (add-on to pioglitazone therapy)
versus
placebo (add-on to pioglitazone therapy)
vildagliptin versus rosiglitazone
Rosenstock, 2009
NCT00138619
vildagliptin (50 mg b.i.d
versus
rosiglitazone (8 mg q.d.,
drug-naïve type 2 diabetes mellitus patientsdouble-blind
Rosenstock* (vilda vs rosi), 2007
NCT00099918
vildagliptin 100 mg daily daily
versus
rosiglitazone 8 mg once daily
drug-naïve patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
vildagliptin versus Sulfonylurea (add on to MET)
Ferrannini, 2009
NCT00106340
vildagliptin 50 mg twice daily
versus
glimepiride titrated up to 6 mg/day
Patients inadequately controlled on metformin monotherapy (HbA(1c) 6.5-8.5%) double-blind
Follow-up duration: 52 weeks
vildagliptin versus TZD (add on MET)
GALIANT (Blonde), 2009
NCT00396227
vildagliptin 100 mg
versus
TZD (agent and dose at the investigators' discretion
patients inadequately controlled [haemoglobin A(1C) (HbA(1c)): 7-10%] on a stable dose of metformin (> or =1000 mg/day).
vildagliptin versus voglibose
Iwamoto, 2010
NA
vildagliptin (50 mg bid,
versus
voglibose (0.2 mg tid
Japanese patients with T2D who were inadequately controlled with diet and exercisedouble-blind
Follow-up duration: 12 weeks
Japan
NCT00368134,
NCT00368134
Vildagliptin 50 mg Bid
versus
Voglibose 0.2 mg Tid
patients with type 2 diabetes
Follow-up duration: 12 weeks
Japan
vildagliptin + MET versus MET
CLAF237A 23104,
NCT00396357

versus
vildagliptin monotherapy versus acarbose
Pan, 2008
NCT00110240
vildagliptin (100 mg daily, given as 50 mg twice daily
versus
acarbose (up to 300 mg daily, given as three equally divided doses
drug-naive patients with Type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
vildagliptin monotherapy versus gliclazide
Foley, 2009
NCT00102388
monotherapy with vildagliptin 50 mg bid
versus
gliclazide up to 320 mg/day
drug-naïve patients with type 2 diabetesdouble-blind
Follow-up duration: 2 years
vildagliptin monotherapy versus pioglitazone
Rosenstock** (vilda vs pio), 2007
NCT00101803
vildagliptin 100 mg daily daily
versus
pioglitazone 30 mg dailyaily
drug-naive patients with type 2 diabetes double-blind
vildagliptin monotherapy versus placebo
Ahren, 2009
NCT00390520
vildagliptin (100 mg/d)
versus
placebo
drug-naive patients with type 2 diabetes
Dejager [1], 2007
NCT00099905
vildagliptin 50 mg or 100 mg daily
versus
placebo
drug-naïve patients with type 2 diabetesdouble-blind
Follow-up duration: 24 weeks
Foley, 2011
NCT00260156
vildagliptin 100 mg
versus
placebo
drug-naive patients with type 2 diabetes and mild hyperglycaemia
Kikuchi, 2009
vildagliptin 50mg bid
versus
placebo
Japanese patients with type 2 diabetes mellitus
Japan
Pi-Sunyer, 2007
NCT00120536
vildagliptin 50 mg or 100 mg daily, imag
versus
placebo
drug-naïve patients with type 2 diabetes double-blind
Follow-up duration: 24 weeks
Pratley, 2006
vildagliptin 25mg bid
versus
placebo
double-blind
Ristic, 2005
vildagliptin 25mg or 50mg or 100mg daily
versus
placebo
voglibose versus placebo
Voglibose Ph-3, 2009
UMIN 000001109-
voglibose 0.2 mg three times daily
versus
placebo
patients with impaired fasting glucosedouble blind
Follow-up duration: 4.01 years
Japan