diabetes - insulin secretagogues peptides (incretins) - all type of patients clinical trials results meta-analysis

<h1> <a href="index.html"> <strong>diabetes</strong> - insulin secretagogues peptides (incretins) </a> - all type of patients trial results systematic overview and meta-analysis </h1> <h2>Main characteristics of the included studies</h2> <table> <tr> <th>Trial</th> <th>Treatments</th> <th>Patients</th> <th>Methods</th> </tr> <tr> <td> <a href="index.html"> Madsbad (vs Glimepiride), 2004 </a> <br> </td> <td> Liraglutide 0.045�0.75 mg daily<br>  <i>versus</i> <br> Glimepiride </td> <td> </td> <td> follow-up 12 weeks<br> n=135/26<br> <br> open <br> </td> </tr> <tr> <td> <a href="index.html"> Vilsboll, 2008 </a> <br> </td> <td> Liraglutide 0.65�1.90 mg daily<br>  <i>versus</i> <br> Placebo </td> <td> patients with Type 2 diabetes </td> <td> follow-up 14 weeks<br> n=123/40<br> parallel groups<br> double blind (not adequate) <br> </td> </tr> <tr> <td> <a href="index.html"> Seino, 2008 </a> <br> NCT00154414 </td> <td> Liraglutide 0.1�0.9 mg daily <br>  <i>versus</i> <br> Placebo </td> <td> Japanese subjects with type 2 diabetes </td> <td> follow-up 14 weeks<br> n=180/46<br> <br> double blind <br> Japan </td> </tr> <tr> <td> <a href="index.html"> Feinglos, 2005 </a> <br> </td> <td> Liraglutide 0.045�0.75 mg daily<br>  <i>versus</i> <br> Metformin </td> <td> subjects with Type 2 diabetes </td> <td> follow-up 12 weeks<br> n=176/34<br> <br> double blind (not adequate) <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-3 mono (Garber), 2009 </a> <br> NCT00294723 </td> <td> Liraglutide 1.2�1.8 mg daily <br>  <i>versus</i> <br> Glimepiride 8 mg once daily or Glimepiride 8 mg once daily </td> <td> subjects with type 2 diabetes </td> <td> follow-up 52 weeks (104 weeks)<br> n=498/248<br> <br> double blind <br> North America </td> </tr> <tr> <td> <a href="index.html"> LEAD-2 (Nauck) (vs placebo), 2009 </a> <br> NCT00318461 </td> <td> Liraglutide 1.2�1.8 mg daily<br>  <i>versus</i> <br> Placebo on-top of Metformin </td> <td> subjects previously treated with oral antidiabetes therapy </td> <td> follow-up 26 weeks<br> n=724/121<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-1, 0 </a> <br> NCT00318422 </td> <td> Liraglutide 1.2�1.8 mg daily <br>  <i>versus</i> <br> Placebo on-top of sulphonylureas </td> <td> </td> <td> follow-up 26 weeks<br> n=695/115<br> <br> not reported <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-4, 0 </a> <br> NCT00333151 </td> <td> Liraglutide 1.2�1.8 mg daily<br>  <i>versus</i> <br> Placebo on-top of thiazolidinediones+metformin </td> <td> </td> <td> follow-up 26 weeks<br> n=356/177<br> <br> not reported <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-5 (vs placebo), 0 </a> <br> NCT00331851 </td> <td> Liraglutide 1.8 mg daily<br>  <i>versus</i> <br> Placebo on-top of sulphonylureas+metformin </td> <td> </td> <td> follow-up 26 weeks<br> n=230/119<br> <br> not reported <br> </td> </tr> <tr> <td> <a href="index.html"> Davis, 2007 </a> <br> NCT00099333 </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Insulin on-top of sulphonylureas/metformin </td> <td> </td> <td> follow-up 16 weeks<br> n=33/16<br> <br> open <br> </td> </tr> <tr> <td> <a href="index.html"> Barnett, 2007 </a> <br> NCT00099619 </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Insulin </td> <td> </td> <td> follow-up 16 weeks<br> n=136/127<br> Cross over<br> open <br> NA </td> </tr> <tr> <td> <a href="index.html"> Nauck, 2007 </a> <br> NCT00082407 </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Insulin on-top of sulphonylureas+metformin </td> <td> </td> <td> follow-up 52 weeks<br> n=253/248<br> <br> open <br> </td> </tr> <tr> <td> <a href="index.html"> Heine, 2005 </a> <br> </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Insulin on-top of sulphonylureas+metformin </td> <td> </td> <td> follow-up 26 weeks<br> n=282/267<br> <br> open <br> </td> </tr> <tr> <td> <a href="index.html"> DeFronzo, 2005 </a> <br> NCT00039013 </td> <td> Exenatide 10�20 �g daily<br>  <i>versus</i> <br> Placebo on-top of Metformin </td> <td> patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses </td> <td> follow-up 30 weeks<br> n=223/113<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> Zinman, 2007 </a> <br> NCT00099320 </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Placebo on-top of thiazolidinediones+/-metformin </td> <td> </td> <td> follow-up 16 weeks<br> n=121/112<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> Buse, 2004 </a> <br> NCT00039026 </td> <td> Exenatide 20 �g daily<br>  <i>versus</i> <br> Placebo on-top of SU </td> <td> patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy </td> <td> follow-up 30 weeks<br> n=248/129<br> <br> double blind (not adequate) <br> </td> </tr> <tr> <td> <a href="index.html"> Kendall, 2005 </a> <br> NCT00035984 </td> <td> Exenatide 10�20 �g daily<br>  <i>versus</i> <br> Placebo on-top of sulphonylureas+metformin </td> <td> patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy </td> <td> follow-up 30 weeks<br> n=486/247<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> Kadowaki (trial 8683), 0 </a> <br> </td> <td> Exenatide 5�10�20 �g daily<br>  <i>versus</i> <br> Placebo on-top of sulphonylureas+/-metformin/thiazolidinediones </td> <td> </td> <td> follow-up 12 weeks<br> n=111/40<br> <br> not reported <br> </td> </tr> <tr> <td> <a href="index.html"> Kim, 2007 </a> <br> NCT00103935 </td> <td> Exenatide 0.8�2 �g daily<br>  <i>versus</i> <br> Placebo on-top of metformin </td> <td> </td> <td> follow-up 15 weeks<br> n=30/15<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> Moretto, 2008 </a> <br> NCT00381342 </td> <td> Exenatide 10�20 �g daily<br>  <i>versus</i> <br> Placebo </td> <td> </td> <td> follow-up 24 weeks<br> n=155/78<br> Parallel groups<br> double blind <br> United States, Puerto Rico, Romania, Russia, India </td> </tr> <tr> <td> <a href="index.html"> Madsbad (vs placebo), 2004 </a> <br> </td> <td> Liraglutide 0.045�0.75 mg daily<br>  <i>versus</i> <br> Placebo </td> <td> </td> <td> follow-up 12 weeks<br> n=135/29<br> <br> open <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-2 (Nauck) (vs glimepiride), 2009 </a> <br> NCT00318461 </td> <td> Liraglutide 1.2�1.8 mg daily<br>  <i>versus</i> <br> Glimepiride on-top of Metformin </td> <td> </td> <td> follow-up 26 weeks<br> n=724/242<br> <br> double blind <br> </td> </tr> <tr> <td> <a href="index.html"> LEAD-5 (vs Glargine), 0 </a> <br> NCT00331851 </td> <td> Liraglutide 1.8 mg daily<br>  <i>versus</i> <br> Glargine on-top of sulphonylureas+metformin </td> <td> </td> <td> follow-up 26 weeks<br> n=230/232<br> <br> not reported <br> </td> </tr> <tr> <td> <a href="index.html"> LEADER, </a> <br> NCT01179048 </td> <td> Maximum dose of 1.8 mg liraglutide, injected subcutaneously once daily<br>  <i>versus</i> <br> placebo </td> <td> subjects with type 2 diabetes </td> <td> follow-up <br> n=-9/-9<br> <br> double-blind <br> Africa, Asia, Europe, North and South America </td> </tr> </table> <h2>References</h2> <p> <b>Madsbad (vs Glimepiride), 2004 : </b> Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DRImproved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. <i>Diabetes Care 2004;27:1335-42</i> [PMID 15161785] </p> <p> <b>Vilsboll, 2008 : </b> Vilsb�ll T, Brock B, Perrild H, Levin K, Lervang HH, K�lendorf K, Krarup T, Schmitz O, Zdravkovic M, Le-Thi T, Madsbad SLiraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. <i>Diabet Med 2008;25:152-6</i> [PMID 18201212] 10.1111/j.1464-5491.2007.02333.x </p> <p> <b>Seino, 2008 : </b> Seino Y, Rasmussen MF, Zdravkovic M, Kaku KDose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: A double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. <i>Diabetes Res Clin Pract 2008;81:161-8</i> [PMID 18495285] 10.1016/j.diabres.2008.03.018 </p> <p> <b>Feinglos, 2005 : </b> Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago OEffects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. <i>Diabet Med 2005;22:1016-23</i> [PMID 16026367] 10.1111/j.1464-5491.2005.01567.x </p> <p> <b>LEAD-3 mono (Garber), 2009 : </b> Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode BLiraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. <i>Lancet 2009;373:473-81</i> [PMID 18819705] 10.1016/S0140-6736(08)61246-5 </p> <p> <b>LEAD-2 (Nauck) (vs placebo), 2009 : </b> Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, D�ring M, Matthews DREfficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. <i>Diabetes Care 2009;32:84-90</i> [PMID 18931095] 10.2337/dc08-1355 </p> <p> <b>LEAD-2 (Nauck) (vs placebo), 2009 : </b> Sullivan SD, Alfonso-Cristancho R, Conner C, Hammer M, Blonde LLong-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone. <i>Cardiovasc Diabetol 2009;8:12</i> [PMID 19245711] 10.1186/1475-2840-8-12 </p> <p> <b>LEAD-2 (Nauck) (vs placebo), 2009 : </b> Nauck M, Marre MAdding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. <i>Postgrad Med 2009;121:5-15</i> [PMID 19491535] 10.3810/pgm.2009.05.1997 </p> <p> <b>LEAD-4, 0 : </b> Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L, , Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). <i>Diabetes Care 2009;32:1224-30.</i> [PMID 19289857] 10.2337/dc08-2124 </p> <p> <b>Davis, 2007 : </b> Davis SN, Johns D, Maggs D, Xu H, Northrup JH, Brodows RGExploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents. <i>Diabetes Care 2007;30:2767-72</i> [PMID 17595353] 10.2337/dc06-2532 </p> <p> <b>Barnett, 2007 : </b> Barnett AH, Burger J, Johns D, Brodows R, Kendall DM, Roberts A, Trautmann METolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. <i>Clin Ther 2007;29:2333-48</i> [PMID 18158075] 10.1016/j.clinthera.2007.11.006 </p> <p> <b>Nauck, 2007 : </b> Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann MA comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. <i>Diabetologia 2007;50:259-67</i> [PMID 17160407] 10.1007/s00125-006-0510-2 </p> <p> <b>Heine, 2005 : </b> Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RGExenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. <i>Ann Intern Med 2005;143:559-69</i> [PMID 16230722] </p> <p> <b>DeFronzo, 2005 : </b> DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron ADEffects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. <i>Diabetes Care 2005;28:1092-100</i> [PMID 15855572] </p> <p> <b>DeFronzo, 2005 : </b> Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DMInterim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. <i>Diabetes Obes Metab 2006;8:436-47</i> [PMID 16776751] 10.1111/j.1463-1326.2006.00602.x </p> <p> <b>DeFronzo, 2005 : </b> Ratner RE, Maggs D, Nielsen LL, Stonehouse AH, Poon T, Zhang B, Bicsak TA, Brodows RG, Kim DDLong-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. <i>Diabetes Obes Metab 2006;8:419-28</i> [PMID 16776749] 10.1111/j.1463-1326.2006.00589.x </p> <p> <b>Zinman, 2007 : </b> Zinman B, Hoogwerf BJ, Dur�n Garc�a S, Milton DR, Giaconia JM, Kim DD, Trautmann ME, Brodows RGThe effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. <i>Ann Intern Med 2007;146:477-85</i> [PMID 17404349] </p> <p> <b>Buse, 2004 : </b> Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron ADEffects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. <i>Diabetes Care 2004;27:2628-35</i> [PMID 15504997] </p> <p> <b>Buse, 2004 : </b> Riddle MC, Henry RR, Poon TH, Zhang B, Mac SM, Holcombe JH, Kim DD, Maggs DGExenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. <i>Diabetes Metab Res Rev 2006;22:483-91</i> [PMID 16634116] 10.1002/dmrr.646 </p> <p> <b>Buse, 2004 : </b> Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DMInterim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. <i>Diabetes Obes Metab 2006;8:436-47</i> [PMID 16776751] 10.1111/j.1463-1326.2006.00602.x </p> <p> <b>Kendall, 2005 : </b> Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron ADEffects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. <i>Diabetes Care 2005;28:1083-91</i> [PMID 15855571] </p> <p> <b>Kadowaki (trial 8683), 0 : </b> Kadowaki T, Namba M, Yamamura A, Sowa H, Wolka AM, Brodows RGExenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes. <i>Endocr J 2009;56:415-24</i> [PMID 19194050] </p> <p> <b>Kim, 2007 : </b> Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, Taylor KEffects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. <i>Diabetes Care 2007;30:1487-93</i> [PMID 17353504] 10.2337/dc06-2375 </p> <p> <b>Moretto, 2008 : </b> Moretto TJ, Milton DR, Ridge TD, Macconell LA, Okerson T, Wolka AM, Brodows RGEfficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. <i>Clin Ther 2008;30:1448-60</i> [PMID 18803987] 10.1016/j.clinthera.2008.08.006 </p> <p> <b>Madsbad (vs placebo), 2004 : </b> Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DRImproved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. <i>Diabetes Care 2004;27:1335-42</i> [PMID 15161785] </p> <p> <b>LEAD-2 (Nauck) (vs glimepiride), 2009 : </b> Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, D�ring M, Matthews DREfficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. <i>Diabetes Care 2009;32:84-90</i> [PMID 18931095] 10.2337/dc08-1355 </p> <p> <b>LEAD-5 (vs Glargine), 0 : </b> Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Sim� R, , Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. <i>Diabetologia 2009;52:2046-55.</i> [PMID 19688338] 10.1007/s00125-009-1472-y </p> <p> <b>LEAD-5 (vs Glargine), 0 : </b> Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Sim� RLiraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. <i>Diabetologia 2009 Oct;52:2046-55</i> [PMID 19688338] </p> <p> <b>LEAD-5 (vs Glargine), 0 : </b> Sullivan SD, Alfonso-Cristancho R, Conner C, Hammer M, Blonde LLong-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone. <i>Cardiovasc Diabetol 2009 Feb 26;8:12</i> [PMID 19245711] </p>