| pathology | treatment | patient | Demonstrated benefit and harm | k | | | |
|---|
| diabetes type 2 | albiglutide | not classified | versus add on oral therapy No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Rosenstock (30 mg weekly), 2009 | albiglutide weekly vs placebo (add on MET) | | | CV events NaN [NaN; NaN] | | Rosenstock (30 mg every two weeks), 2009 | albiglutide biweekly vs placebo (add on MET) | | | CV events ∞ [NaN; ∞] |
| Trial | Treatments | Patients | Method |
|---|
| Rosenstock (30 mg weekly), 2009 | albiglutide
30mg weekly (n=31) vs. placebo (n=52) 8 arms with liraglutide and 1 arm with exenatide twice daily (+1 arm receiving placebo): albiglutide
weekly (4, 15, or 30 mg), every 2 weeks
(biweekly; 15, 30, or 50 mg), or monthly
(50 or 100 mg) | patients with type 2 diabetes inadequately controlled with diet and exercise or
metformin monotherapy | double-blind Parallel groups Sample size: 31/52 Primary endpoint: FU duration: 16 weeks phase 2 | | Rosenstock (30 mg every two weeks), 2009 | albiglutide
30mg weekly
(n=32) vs. placebo
(n=50) 8 arms with liraglutide and 1 arm with exenatide twice daily (+1 arm receiving placebo): albiglutide
weekly (4, 15, or 30 mg), every 2 weeks
(biweekly; 15, 30, or 50 mg), or monthly
(50 or 100 mg)
| patients with type 2 diabetes inadequately controlled with diet and exercise or
metformin monotherapy
| double blind Parallel groups Sample size: 32/50 Primary endpoint: 0 FU duration: 16 weeks phase 2
|
|
| diabetes type 2 | albiglutide | not classified | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Seino, 2009 | albiglutide vs placebo | | | nausea ∞ [NaN; ∞] vomiting ∞ [NaN; ∞] diarrhoea ∞ [NaN; ∞] treatment-emergent
adverse events (TEAEs) 2.25 [0.33; 15.27] |
| Trial | Treatments | Patients | Method |
|---|
| Seino, 2009 | albiglutide 15 mg weekly, 30 mg weekly, 50 mg biweekly, and
100 mg monthly (n=32) vs. placebo (n=8) | Japanese subjects
with type 2 diabetes mellitus | single-blind Parallel groups Sample size: 32/8 Primary endpoint: not unique FU duration: 4 weeks (+5 wk) phase 2 |
|
| diabetes type 2 | exenatide | not classified | versus No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Exenatide Trial 10749 | exenatide before lunch and dinner vs exenatide before breakfast and dinner | | | | | phase 2 exenatide once monthly | exenatide once monthly vs weekly exenatide | | | | | Drucker, 2008 | exenatide 20µg/d vs weekly exenatide | | | | | H8O-MC-GWBJ, 9698, 10µg/d, 2008 | exenatide 10µg/d vs placebo | | | | | Liutkus, 2010 | exenatide vs placebo | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Exenatide Trial 10749 | exenatide (10 ìg twice daily)
administered subcutaneously before lunch and dinner (n=187) vs. exenatide (10 ìg twice daily)
administered subcutaneously before breakfast and dinner (n=190) | patients with type 2 Diabetes using oral antidiabetic therapy | open Parallel groups Sample size: 187/190 Primary endpoint: FU duration: phase 3b | | 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 (n=121) vs. exenatide 2mg once weekly (n=0) | 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 both | open Parallel groups Sample size: 121/0 Primary endpoint: FU duration: 20 weeks phase 2 | | Drucker, 2008 | 10 mug exenatide administered twice a day (n=-9) vs. long-acting release formulation of exenatide 2 mg administered once weekly (n=-9) | patients with type 2 diabetes naive to drug therapy, or on one or more oral antidiabetic agents | open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 30 weeks | | H8O-MC-GWBJ, 9698, 10µg/d, 2008 | exenatide twice daily 5 et 10 µg for 24 weeks
(n=-9) vs. placebo
(n=78) 3 arms: exenatide 5µg BID, 10µg bid, placebo
| Drug-Naive Patients with Type 2 Diabetes and inadequate glycemic control through diet and exercise
| double-blind Parallel groups Sample size: -9/78 Primary endpoint: change in HbA1c FU duration: 24 weeks
| | Liutkus, 2010 | exenatide twice-daily (n=111) vs. placebo (n=54) | subjects suboptimally controlled with TZDs with or without metformin | Sample size: 111/54 Primary endpoint: FU duration: |
|
| diabetes type 2 | exenatide | not classified | versus add on insulin No demonstrated result for efficacy exenatide 20µg/d inferior to placebo (add on insulin) in terms of nausea in Buse, 2011 exenatide 20µg/d inferior to placebo (add on insulin) in terms of vomiting in Buse, 2011 exenatide 20µg/d inferior to placebo (add on insulin) in terms of diarrhoea in Buse, 2011 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Buse, 2011 | exenatide 20µg/d vs placebo (add on insulin) | | nausea 4.99 [2.66; 9.34] vomiting 4.45 [1.76; 11.27] diarrhoea 2.23 [1.11; 4.45] | death 0.00 [0.00; NaN] severe hypoglycemia 0.00 [0.00; NaN] treatment-emergent
adverse events (TEAEs) 1.13 [0.98; 1.30] severe adverse events 0.65 [0.27; 1.56] |
| Trial | Treatments | Patients | Method |
|---|
| Buse, 2011 | twice-daily 10 µg exenatide injections (n=138) vs. placebo (on top insulin glargine) (n=123) | 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 Parallel groups Sample size: 138/123 Primary endpoint: change in HbA1c FU duration: 30 weeks |
|
| diabetes type 2 | exenatide | not classified | versus placebo No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Apovian, 2010 | exenatide 20µg/d vs placebo | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Apovian, 2010 | 10 microg exenatide twice daily injection + lifestyle modification program (n=96) vs. placebo + lifestyle modification program (n=98) | overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylurea | double-blind Parallel groups Sample size: 96/98 Primary endpoint: FU duration: 24 weeks |
|
| diabetes type 2 | exenatide | not classified | versus placebo or control No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Moretto (DOUBLONS avec druker), 2008 | exenatide other doses vs placebo | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] nausea ∞ [NaN; ∞] vomiting ∞ [NaN; ∞] diarrhoea ∞ [NaN; ∞] severe hypoglycemia NaN [NaN; NaN] ant hypoglycemia 3.52 [0.44; 28.13] | | NCT00085969 | exenatide other doses vs placebo | | | | | Poon, 2005 | exenatide other doses vs placebo | | | | | H8O-MC-GWBJ, 9698, 20µg/d, 2008 | exenatide 20µg/d vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Moretto (DOUBLONS avec druker), 2008 | Exenatide 10–20 µg daily (n=155) vs. Placebo (n=78) | | double blind Parallel groups Sample size: 155/78 Primary endpoint: FU duration: 24 weeks | | NCT00085969 | exenatide for 28 days (n=99) vs. placebo (n=0) Subjects were randomly assigned to one of six treatment groups (A1, A2, A3, B, C, or D). Subjects assigned
to exenatide groups B, C, and D received 10 ìg twice daily (BID) (group B), 10 ìg once daily (QD)
(group C), or 20 ìg QD (group D) during the 4-week, triple-blind treatment period. Subjects assigned to
placebo groups A1, A2, and A3 received placebo BID (A1) or QD (A2, A3) in dose volumes equivalent to
those received by groups B, C, and D, respectively. | subjects with type 2 diabetes mellitus | double-blind Sample size: 99/0 Primary endpoint: HbA1c change FU duration: 28 days phase 2 | | Poon, 2005 | exenatide at 2.5, 5.0, 7.5, or 10.0 microg administered b.i.d. for 28 days (n=-9) vs. placebo (n=-9) | patients with type 2 diabetes | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: not defined FU duration: 28 days dose-ranging study | | H8O-MC-GWBJ, 9698, 20µg/d, 2008 | exenatide twice daily 10 µg for 24 weeks (n=78) vs. placebo (n=78) 3 arms: exenatide 5µg BID, 10µg bid, placebo | Drug-Naive Patients with Type 2 Diabetes and inadequate glycemic control through diet and exercise | double-blind Parallel groups Sample size: 78/78 Primary endpoint: change in HbA1c FU duration: 24 weeks |
|
| diabetes type 2 | exenatide | not classified | versus add on oral therapy No demonstrated result for efficacy exenatide 20µg/d inferior to insulin (add on SU/MET) in terms of nausea in Davis, 2007 exenatide 20µg/d inferior to insulin BIAsp twice daily add on SU+MET in terms of nausea in Nauck, 2007 exenatide 20µg/d inferior to insulin BIAsp twice daily add on SU+MET in terms of vomiting in Nauck, 2007 exenatide 20µg/d inferior to insulin BIAsp twice daily add on SU+MET in terms of diarrhoea in Nauck, 2007 exenatide 20µg/d inferior to insulin BIAsp twice daily add on SU+MET in terms of treatment-emergent
adverse events (TEAEs) in Nauck, 2007 exenatide 20µg/d inferior to insulin (add on SU+MET) in terms of nausea in Heine, 2005 exenatide 20µg/d inferior to insulin (add on SU+MET) in terms of vomiting in Heine, 2005 exenatide 20µg/d inferior to insulin (add on SU+MET) in terms of diarrhoea in Heine, 2005 exenatide 10µg/d inferior to placebo (add on MET) in terms of nausea in DeFronzo 10µg/d, 2005 exenatide 10µg/d inferior to placebo (add on MET) in terms of vomiting in DeFronzo 10µg/d, 2005 exenatide 20µg/d inferior to placebo (add on TZD+/-MET) in terms of nausea in Zinman 20µg/j, 2007 exenatide 20µg/d inferior to placebo (add on TZD+/-MET) in terms of vomiting in Zinman 20µg/j, 2007 exenatide 10µg/d inferior to placebo (add on SU) in terms of nausea in Buse 10µg/d, 2004 exenatide 10µg/d inferior to placebo (add on SU) in terms of vomiting in Buse 10µg/d, 2004 exenatide 10µg/d inferior to placebo (add on SU) in terms of diarrhoea in Buse 10µg/d, 2004 exenatide 20µg/d inferior to placebo (add on SU+MET) in terms of nausea in Kendall 20µg/d, 2005 exenatide 20µg/d inferior to placebo (add on SU+MET) in terms of vomiting in Kendall 20µg/d, 2005 exenatide 20µg/d inferior to placebo (add on SU+MET) in terms of diarrhoea in Kendall 20µg/d, 2005 exenatide 20µg/d inferior to placebo (add on SU+MET) in terms of ant hypoglycemia in Kendall 20µg/d, 2005 exenatide 20µg/d inferior to placebo (add on MET+/-SU) in terms of nausea in Gao, 2009 exenatide 20µg/d inferior to placebo (add on MET+/-SU) in terms of ant hypoglycemia in Gao, 2009 exenatide 20µg/d inferior to placebo (add on MET+/-SU) in terms of treatment-emergent
adverse events (TEAEs) in Gao, 2009 exenatide 10µg/d inferior to placebo (add on SU+MET) in terms of nausea in Kendall 10µg/d, 2005 exenatide 10µg/d inferior to placebo (add on SU+MET) in terms of vomiting in Kendall 10µg/d, 2005 | 16 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Davis, 2007 | exenatide 20µg/d vs insulin (add on SU/MET) | | nausea 3.88 [1.01; 14.86] | death NaN [NaN; NaN] CV events ∞ [NaN; ∞] vomiting 3.88 [0.53; 28.41] diarrhoea ∞ [NaN; ∞] severe hypoglycemia ∞ [NaN; ∞] ant hypoglycemia 1.05 [0.49; 2.25] treatment-emergent
adverse events (TEAEs) 1.40 [0.88; 2.23] | | Nauck, 2007 | exenatide 20µg/d vs insulin BIAsp twice daily add on SU+MET | | nausea 82.34 [11.55; 586.81] vomiting 4.66 [2.22; 9.78] diarrhoea 4.71 [1.82; 12.14] treatment-emergent
adverse events (TEAEs) 1.43 [1.23; 1.65] | death 1.96 [0.18; 21.48] CV deaths 0.98 [0.06; 15.59] CV events 1.96 [0.68; 5.65] severe hypoglycemia NaN [NaN; NaN] serious adverse events 1.69 [0.82; 3.48] | | Heine, 2005 | exenatide 20µg/d vs insulin (add on SU+MET) | | nausea 6.63 [4.43; 9.92] vomiting 4.64 [2.40; 8.97] diarrhoea 2.84 [1.30; 6.21] | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events 1.58 [0.38; 6.54] severe hypoglycemia 0.95 [0.24; 3.75] | | DeFronzo 10µg/d, 2005 | exenatide 10µg/d vs placebo (add on MET) | | nausea 1.58 [1.04; 2.40] vomiting 3.08 [1.03; 9.27] | death NaN [NaN; NaN] diarrhoea 1.48 [0.66; 3.33] severe hypoglycemia NaN [NaN; NaN] | | Zinman 20µg/j, 2007 | exenatide 20µg/d vs placebo (add on TZD+/-MET) | | nausea 2.61 [1.60; 4.27] vomiting 14.81 [2.00; 109.86] | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] diarrhoea 2.16 [0.57; 8.15] ant hypoglycemia 1.50 [0.65; 3.49] | | Buse 10µg/d, 2004 | exenatide 10µg/d vs placebo (add on SU) | | nausea 5.36 [2.75; 10.43] vomiting 3.94 [1.14; 13.61] diarrhoea 2.76 [1.02; 7.42] | death NaN [NaN; NaN] severe hypoglycemia NaN [NaN; NaN] | | Kendall 20µg/d, 2005 | exenatide 20µg/d vs placebo (add on SU+MET) | | nausea 2.35 [1.78; 3.10] vomiting 3.07 [1.59; 5.94] diarrhoea 2.69 [1.56; 4.65] ant hypoglycemia 3.77 [2.64; 5.38] | death 0.00 [0.00; NaN] severe hypoglycemia ∞ [NaN; ∞] | | Kadowaki (trial 8683), 2009 | exenatide 10µg/d vs placebo (add on SU+/-MET/TZD) | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] nausea ∞ [NaN; ∞] severe hypoglycemia NaN [NaN; NaN] | | Kim, 2007 | exenatide weekly vs placebo (add on MET) | | | death NaN [NaN; NaN] CV events NaN [NaN; NaN] nausea 3.50 [0.47; 25.90] vomiting NaN [NaN; NaN] severe hypoglycemia NaN [NaN; NaN] ant hypoglycemia ∞ [NaN; ∞] | | Fineman, 2003 | exenatide other doses vs placebo (add on MER+/-SU) | | | | | Zinman 20µg/j A MODIFIER, 2007 | exenatide 20µg/d vs placebo (add on TZD+/-MET) | | | | | Gao, 2009 | exenatide 20µg/d vs placebo (add on MET+/-SU) | | nausea 29.25 [7.23; 118.31] ant hypoglycemia 3.92 [2.52; 6.10] treatment-emergent
adverse events (TEAEs) 1.58 [1.29; 1.94] | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events 0.00 [0.00; NaN] vomiting ∞ [NaN; ∞] diarrhoea 1.49 [0.54; 4.11] severe hypoglycemia 1.98 [0.18; 21.72] | | DeFronzo 20µg/d, 2005 | exenatide 20µg/d vs placebo (add on MET) | | | | | Buse 20µg/d, 2004 | exenatide 20µg/d vs placebo (add on SU) | | | | | Kendall 10µg/d, 2005 | exenatide 10µg/d vs placebo (add on SU+MET) | | nausea 1.90 [1.42; 2.54] vomiting 3.30 [1.72; 6.33] | diarrhoea 1.58 [0.86; 2.88] | | Gill, 2010 | exenatide 10µg/d vs placebo add on MET+/-TZD | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Davis, 2007 | Exenatide 20 µg daily (n=33) vs. Insulin on-top of sulphonylureas/metformin (n=16) | patients with type 2 diabetes using insulin in combination with oral antidiabetes agents | open Parallel groups Sample size: 33/16 Primary endpoint: glycemic control FU duration: 16 weeks | | Nauck, 2007 | Exenatide 20 µg daily (n=253) vs. Insulin on-top of sulphonylureas+metformin (n=248) | patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin | open Parallel groups Sample size: 253/248 Primary endpoint: HbA1c FU duration: 52 weeks | | Heine, 2005 | Exenatide 20 µg daily (n=282) vs. Insulin on-top of sulphonylureas+metformin (n=267) | | open Sample size: 282/267 Primary endpoint: FU duration: 26 weeks | | DeFronzo 10µg/d, 2005 | Exenatide 10–20 µg daily (n=110) vs. Placebo on-top of Metformin (n=113) 3 arms : exenatide 5µg twice daily, 10µg twice daily and placebo | patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses | double blind Parallel groups Sample size: 110/113 Primary endpoint: HbA1c FU duration: 30 weeks | | Zinman 20µg/j, 2007 | Exenatide 20 µg daily
(n=121) vs. Placebo on-top of thiazolidinediones+/-metformin
(n=112)
| patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin)
| double blind Sample size: 121/112 Primary endpoint: FU duration: 16 weeks
| | Buse 10µg/d, 2004 | Exenatide 5µg twice daily (n=125) vs. Placebo on-top of SU (n=123) 3rd arms with exenatide 10µg BID | patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy | double blind (not adequate) Parallel groups Sample size: 125/123 Primary endpoint: HbA1c FU duration: 30 weeks | | Kendall 20µg/d, 2005 | Exenatide 10 µg bid (n=241) vs. Placebo on-top of sulphonylureas+metformin (n=247) 3 arms: exenatide 5, 10µg bid or placebo | patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy | double blind Parallel groups Sample size: 241/247 Primary endpoint: change in HbA1c FU duration: 30 weeks | | Kadowaki (trial 8683), 2009 | Exenatide 10µg daily for 12 weeks (n=111) vs. Placebo on-top of sulphonylureas +/-metformin/thiazolidinediones (n=40) Exenatide 5–10–20 µg daily for 12 weeks | Japanese patients with type 2 diabetes suboptimally controlled despite therapeutic dose of sulfonylurea, SU+biguanide or SU+thiazolidinedione | open Parallel groups Sample size: 111/40 Primary endpoint: change in HbA1c FU duration: 12 weeks | | Kim, 2007 | exenatide LAR 0.8 or 2 µg daily (n=30) vs. Placebo on-top of metformin (n=15) | subjects with type 2 diabetes suboptimally controlled with metformin and/or diet and exercise | double blind Parallel groups Sample size: 30/15 Primary endpoint: not defined FU duration: 15 weeks | | Fineman, 2003 | exenatide 3 regimen (0.08 micro g/kg) for 28 days (n=109) vs. placebo (n=0) 4 arms: three subcutaneously injected regimens of AC2993 or placebo | patients with tyep 2 diabetes treated with diet and a sulfonylurea and/or metformin | double-blind Parallel groups Sample size: 109/0 Primary endpoint: not defined FU duration: 28 days phase 2 | | Zinman 20µg/j A MODIFIER, 2007 | exenatide Subcutaneous abdominal injections of 10 microg twice daily (n=121) vs. placebo (n=112) | patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin) | double-blind Parallel groups Sample size: 121/112 Primary endpoint: change from baseline in hemoglobin A1c FU duration: 16 weeks | | Gao, 2009 | exenatide 5 mg then 10 mg twice-daily for 4 and 12 weeks (n=234) vs. placebo
(n=232)
| Asian desccent with type 2 diabetes and inadequate glycemic control taking
metformin alone or Met and sulfonylureas
| double-blind Parallel groups Sample size: 234/232 Primary endpoint: change in HbA1c FU duration: 16 weeks phase 3
| | DeFronzo 20µg/d, 2005 | Exenatide 10–20 µg daily (n=-9) vs. Placebo on-top of Metformin (n=113) 3 arms : exenatide 5µg twice daily, 10µg twice daily and placebo
| patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses
| double blind Parallel groups Sample size: -9/113 Primary endpoint: HbA1c FU duration: 30 weeks
| | Buse 20µg/d, 2004 | Exenatide 10µg twice daily
(n=129) vs. Placebo on-top of SU
(n=123) 3rd arms with exenatide 5µg BID
| patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy
| double blind (not adequate) Sample size: 129/123 Primary endpoint: HbA1c FU duration: 30 weeks
| | Kendall 10µg/d, 2005 | Exenatide 5 µg bid
(n=245) vs. Placebo on-top of sulphonylureas+metformin
(n=247) 3 arms: exenatide 5, 10µg bid or placebo
| patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy
| double blind Parallel groups Sample size: 245/247 Primary endpoint: change in HbA1c FU duration: 30 weeks
| | Gill, 2010 | exenatide (5 microg for 4 weeks followed by 10 microg) for 12 weeks (n=28) vs. placebo (n=26) | subjects with type 2 diabetes mellitus on metformin and/or a thiazolidinedione | double-blind Parallel groups Sample size: 28/26 Primary endpoint: mean 24-hour HR FU duration: 12 weeks |
|
| diabetes type 2 | exenatide | not classified | versus glitazone No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DeFronzo (EXE vs ROSI), 2010 | exenatide 20µg/d vs rosiglitazone add on MET | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| DeFronzo (EXE vs ROSI), 2010 | EXE 10 microg b.i.d. (n=45) vs. ROSI 4 mg b.i.d. (n=45) 3 arms: EXE 10 microg bid (n=45), ROSI 4 mg bid (n=45), or EXE 10 microg bid + ROSI 4 mg bid (n=47) | subjects with type 2 diabetes on metformin | open Parallel groups Sample size: 45/45 Primary endpoint: FU duration: 20 weeks |
|
| diabetes type 2 | exenatide | not classified | versus insulin No demonstrated result for efficacy exenatide 20µg/d inferior to insulin (add on SU/MET) in terms of nausea in Barnett, 2007 exenatide 20µg/d inferior to insulin (add on SU/MET) in terms of vomiting in Barnett, 2007 exenatide weekly inferior to insulin glargine in terms of nausea in DURATION-3 (Diamant), 2010 exenatide weekly inferior to insulin glargine in terms of diarrhoea in DURATION-3 (Diamant), 2010 | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Barnett, 2007 | exenatide 20µg/d vs insulin (add on SU/MET) | ant hypoglycemia 0.58 [0.35; 0.97] | nausea 13.54 [5.06; 36.22] vomiting 3.03 [1.02; 9.07] | death NaN [NaN; NaN] CV events NaN [NaN; NaN] diarrhoea 1.25 [0.28; 5.45] severe hypoglycemia 0.00 [0.00; NaN] | | DURATION-3 (Diamant), 2010 | exenatide weekly vs insulin glargine | | nausea 9.57 [2.96; 30.92] diarrhoea 2.39 [1.08; 5.32] | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] CV events ∞ [NaN; ∞] vomiting 3.19 [0.89; 11.44] treatment-emergent
adverse events (TEAEs) 1.14 [1.00; 1.30] serious adverse events 1.05 [0.46; 2.43] | | Trial 8078 | exenatide other doses vs insulin glargine (add on MET/SU) | | | | | Bergenstal (once daily), 2009 | exenatide 20µg/d vs BIAsp 30 daily | | | | | Bergenstal (twice daily), 2009 | exenatide 20µg/d vs BIAsp 30 twice daily | | | | | Bunck, 2009 | exenatide 20µg/d vs insulin glargine (add on MET) | | | | | HEELA (Davies), 2009 | exenatide other doses vs glargine | | | | | NCT00360334 | exenatide vs glargine | | | CV events 0.98 [0.14; 6.86] |
| Trial | Treatments | Patients | Method |
|---|
| Barnett, 2007 | Exenatide 20 µg daily (n=136) vs. Insulin (n=127) | patients with type 2 diabetes | open Cross over Sample size: 136/127 Primary endpoint: HbA1c change FU duration: 16 weeks | | DURATION-3 (Diamant), 2010 | exenatide (2 mg, once-a-week injection) (n=233) vs. insulin glargine once-daily injection (n=223) | 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 longer | open (blind analysis) Parallel groups Sample size: 233/223 Primary endpoint: HbA1c FU duration: 26 weeks | | Trial 8078 | exenatide (n=-9) vs. Insulin Glargine (n=-9) | Patients with Type 2 Diabetes Using Metformin or Sulfonylurea for Whom Insulin Is the Next Appropriate Therapy | Sample size: -9/-9 Primary endpoint: FU duration: | | Bergenstal (once daily), 2009 | exenatide(5 microg BID for 4 weeks and 10 microg BID thereafter) (n=-9) vs. biphasic insulin aspart 70/30 (BIAsp 30) 30 QD (12 U before supper) (n=-9) | subjects with type 2 diabetes mellitus insulin naive, not achieving glycemic targets with metformin and sulfonylurea | open Parallel groups Sample size: -9/-9 Primary endpoint: not unique FU duration: 24 weeks | | Bergenstal (twice daily), 2009 | exenatide (5 microg BID for 4 weeks and 10 microg BID thereafter) (n=-9) vs. biphasic insulin aspart 70/30 (BIAsp 30) 30 BID (12 U divided equally between pre-breakfast and pre-supper) (n=-9)
| subjects with type 2 diabetes mellitus insulin naive, not achieving glycemic targets with metformin and sulfonylurea
| open Parallel groups Sample size: -9/-9 Primary endpoint: not unique FU duration:
| | Bunck, 2009 | exenatide 10µg bid (n=36) vs. insulin glargine (n=33) | metformin-treated patients with type 2 diabetes | Parallel groups Sample size: 36/33 Primary endpoint: beta-Cell function FU duration: 52 weeks | | HEELA (Davies), 2009 | exenatide 5¨C10 ¦Ìg
bid (n=-9) vs. insulin glargine o.d. (titrated to target fasting plasma glucose ¡Ü5.6 mmol/l) (n=-9) | Patients (BMI>27 kg/m2) with elevated cardiovascular risk and type 2 diabetes
inadequately controlled on two or three oral antidiabetes drugs | Sample size: -9/-9 Primary endpoint: FU duration: | | NCT00360334 | (n=118) vs. (n=116) | | Sample size: 118/116 Primary endpoint: FU duration: |
|
| diabetes type 2 | exenatide | not classified | versus oral therapy No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DURATION-2 (Bergenstal) (vs sitagliptin), 2010 | exenatide weekly vs sitagliptin | | | CV events 0.00 [0.00; NaN] | | DURATION-2 (Bergenstal) (vs pioglitazone), 2010 | exenatide weekly vs pioglitazone | | | CV events 0.00 [0.00; NaN] | | DeFronzo, 2008 | exenatide 20µg/d vs sitagliptin (add on MET) | | | | | LEAD 6 (Buse) exe vs lira, 2009 | exenatide 10µg twice daily vs liraglutide 1.8mg | | | | | Derosa, 2010 | exenatide 20µg vs glibenclamide | | | death NaN [NaN; NaN] CV deaths NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| DURATION-2 (Bergenstal) (vs sitagliptin), 2010 | 2 mg injected exenatide once weekly plus oral placebo once daily
(n=170) vs. 100 mg oral sitagliptin once daily plus injected placebo once weekly
(n=-9) 3rd arms receiving 45 mg oral pioglitazone once daily plus injected placebo once weekly
| patients treated with metformin
| double blind Sample size: 170/-9 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | DURATION-2 (Bergenstal) (vs pioglitazone), 2010 | 2 mg injected exenatide once weekly plus oral placebo once daily (n=170) vs. 45 mg oral pioglitazone once daily plus injected placebo once weekly (n=172) 3rd arms receiving 100 mg oral sitagliptin once daily plus injected placebo once weekly
|
| double blind Parallel groups Sample size: 170/172 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | DeFronzo, 2008 | exenatide subcutaneous injection (n=-9) vs. sitagliptin (100 mg QAM) for 2 weeks (n=-9) | metformin-treated T2D patients | double-blind Cross over Sample size: -9/-9 Primary endpoint: not unique FU duration: 2 weeks phase 4 | | LEAD 6 (Buse) exe vs lira, 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Derosa, 2010 | exenatide 10 microg twice a day (n=63) vs. glibenclamide 5 mg three times a day (n=65) | patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin | Sample size: 63/65 Primary endpoint: FU duration: |
|
| diabetes type 2 | liraglutide | not classified | versus No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| NN2211-1333 | liraglutide other doses vs | | | | | Kaku 0.6mg, 2010 | liraglutide other doses vs placebo | | | | | Pratley (1.8 vs 1.2), 2010 | liraglutide 1.8mg vs liraglutide 1.2mg | | | CV events 1.00 [0.06; 15.89] |
| Trial | Treatments | Patients | Method |
|---|
| NN2211-1333 | liraglutide (n=-9) vs. placebo (n=-9) | obese subjects with type 2 diabetes | Sample size: -9/-9 Primary endpoint: FU duration: | | Kaku 0.6mg, 2010 | liraglutide 0.6 mg/day (n=88) vs. placebo (n=88) 3 arms:liraglutide 0.6 mg/day, 0.9 mg/day or placebo | Japanese patients with type 2 diabetes | double-blind Parallel groups Sample size: 88/88 Primary endpoint: FU duration: 24 weeks | | Pratley (1.8 vs 1.2), 2010 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | liraglutide | not classified | versus placebo liraglutide superior to placebo in terms of CV events in LEADER, 2016 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| LEADER, 2016 | liraglutide vs placebo | CV events 0.88 [0.79; 0.97] Demonstrated all causes death 0.85 [0.75; 0.97] CVdeath 0.79 [0.66; 0.94] Microvascular event 0.85 [0.75; 0.98] Nephropathy 0.80 [0.68; 0.93] | | fatal and non fatal stroke 0.87 [0.71; 1.06] fatal and non fatal MI 0.86 [0.74; 1.00] Hospitalization for heart failure 0.88 [0.74; 1.05] Retinopathy 1.15 [0.87; 1.52] |
| Trial | Treatments | Patients | Method |
|---|
| LEADER, 2016 | Maximum dose of 1.8 mg liraglutide, injected subcutaneously once daily (n=4668) vs. placebo (n=4672) | subjects with type 2 diabetes | double-blind Sample size: 4668/4672 Primary endpoint: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke FU duration: 3.8 years (median) |
|
| diabetes type 2 | liraglutide | not classified | versus placebo or control No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Seino, 2008 | liraglutide other doses vs placebo | | | death NaN [NaN; NaN] CV events NaN [NaN; NaN] severe hypoglycemia NaN [NaN; NaN] ant hypoglycemia NaN [NaN; NaN] | | Madsbad (vs placebo), 2004 | liraglutide other doses vs placebo | | | death NaN [NaN; NaN] CV events NaN [NaN; NaN] vomiting ∞ [NaN; ∞] diarrhoea ∞ [NaN; ∞] severe hypoglycemia NaN [NaN; NaN] ant hypoglycemia ∞ [NaN; ∞] | | Harder, 2004 | liraglutide other doses vs placebo | | | | | NN2211-1571 (Vilsbøll), 2007 | liraglutide other doses vs placebo | | | CV events NaN [NaN; NaN] nausea 2.93 [0.38; 22.40] vomiting ∞ [NaN; ∞] diarrhoea 1.69 [0.70; 4.11] |
| Trial | Treatments | Patients | Method |
|---|
| Seino, 2008 | Liraglutide 0.1, 0.3, 0.6 or 0.9 mg once daily for 14 weeks
(n=180) vs. Placebo
(n=46) randomized after OAD discontinuation and washout | Japanese subjects with type 2 diabetes
| double blind Parallel groups Sample size: 180/46 Primary endpoint: HbA1c FU duration: 14 weeks phase 2
| | Madsbad (vs placebo), 2004 | Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily
(n=135) vs. Placebo
(n=29)
| Outpatients with type 2 diabetes
| open Sample size: 135/29 Primary endpoint: change in HbA1c FU duration: 12 weeks dose-response study
| | Harder, 2004 | single daily subcutaneous dose of 0.6 mg liraglutide for 8 weeks (n=21) vs. placebo (n=12) | obese subjects with type 2 diabetes | double-blind Parallel groups Sample size: 21/12 Primary endpoint: not defined FU duration: 8 weeks | | NN2211-1571 (Vilsbøll), 2007 | liraglutide 0.65 mg, 1.25 mg or 1.9 mg for 14 weeks
(n=123) vs. placebo
(n=40)
| subjects with type 2 diabetes
| double-blind Parallel groups Sample size: 123/40 Primary endpoint: not unique FU duration: 14 weeks phase 2, dose ranging
|
|
| diabetes type 2 | liraglutide | not classified | versus add on oral therapy No demonstrated result for efficacy liraglutide 1.2mg inferior to placebo (add on MET) in terms of vomiting in LEAD-2 (Nauck) (1.2mg vs placebo), 2009 liraglutide 1.2mg inferior to placebo (add on SU) in terms of nausea in LEAD-1 SU (1.2 mg vs placebo), 2009 liraglutide 1.8mg inferior to placebo (add on SU+MET) in terms of nausea in LEAD-5 (vs placebo), 2009 liraglutide 1.8mg inferior to placebo (add on SU+MET) in terms of diarrhoea in LEAD-5 (vs placebo), 2009 liraglutide 1.8mg inferior to insulin glargine (add on SU+MET) in terms of nausea in LEAD-5 (vs Glargine), 2009 liraglutide 1.8mg inferior to insulin glargine (add on SU+MET) in terms of vomiting in LEAD-5 (vs Glargine), 2009 liraglutide 1.8mg inferior to insulin glargine (add on SU+MET) in terms of diarrhoea in LEAD-5 (vs Glargine), 2009 | 13 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| LEAD-2 (Nauck) (1.2mg vs placebo), 2009 | liraglutide 1.2mg vs placebo (add on MET) | | vomiting 22.27 [3.11; 159.74] | death NaN [NaN; NaN] severe hypoglycemia NaN [NaN; NaN] | | LEAD-1 SU (1.2 mg vs placebo), 2009 | liraglutide 1.2mg vs placebo (add on SU) | | nausea 4.30 [1.06; 17.42] | severe hypoglycemia ∞ [NaN; ∞] | | LEAD-4 (1.2mg), 2009 | liraglutide 1.2mg vs placebo (add on TZD+MET) | | | CV events 1.24 [0.34; 4.55] severe hypoglycemia NaN [NaN; NaN] | | LEAD-5 (vs placebo), 2009 | liraglutide 1.8mg vs placebo (add on SU+MET) | | nausea 3.97 [1.44; 10.94] diarrhoea 3.80 [1.17; 12.39] | CV events 2.48 [0.29; 20.97] vomiting 1.86 [0.63; 5.47] | | LEAD-2 (Nauck) (1.2 mg vs glimepiride), 2009 | liraglutide 1.2mg vs glimepiride (add on MET) | | | death NaN [NaN; NaN] severe hypoglycemia NaN [NaN; NaN] | | LEAD-5 (vs Glargine), 2009 | liraglutide 1.8mg vs insulin glargine (add on SU+MET) | | nausea 10.76 [3.34; 34.64] vomiting 15.13 [2.02; 113.61] diarrhoea 7.73 [2.35; 25.40] | | | NN2211-1796 | liraglutide other doses vs placebo (add on MET) | | | | | LEAD-4 (1.8mg), 2009 | liraglutide 1.8mg vs placebo (add on TZD+MET) | | | CV events 0.75 [0.17; 3.28] | | LEAD-1 SU (1.8 mg vs placebo), 2009 | liraglutide 1.8mg vs placebo (add on SU) | | | | | LEAD-1 SU (1.8 vs rosiglitazone), 2009 | liraglutide other doses vs rosiglitazone (add on SU) | | | | | LEAD-2 (Nauck) (1.8 mg vs glimepiride), 2009 | liraglutide 1.8mg vs glimepiride (add on MET) | | | | | LEAD-2 (Nauck) (1.8mg vs placebo), 2009 | liraglutide 1.8mg vs placebo (add on MET) | | | | | Kaku 0.9mg, 2010 | liraglutide other doses vs placebo (on top SU) | | | |
| Trial | Treatments | Patients | Method |
|---|
| LEAD-2 (Nauck) (1.2mg vs placebo), 2009 | Liraglutide 1.2 mg daily
(n=241) vs. Placebo on-top of Metformin
(n=122) 5 arms : liraglutide 0.6, 1.2 or 1.8 mg, glimeripide 4mg once daily or placebo
| subjects previously treated with oral antidiabetes therapy
| double blind Parallel groups Sample size: 241/122 Primary endpoint: change in A1C FU duration: 26 weeks
| | LEAD-1 SU (1.2 mg vs placebo), 2009 | Liraglutide 1.2 mg daily
(n=228) vs. Placebo on-top of sulphonylureas
(n=115) 5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo | subjects with
Type 2 diabetes
| double-blind Parallel groups Sample size: 228/115 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | LEAD-4 (1.2mg), 2009 | Liraglutide 1.2 daily (n=178) vs. Placebo on-top of thiazolidinediones + metformin (n=177) 3 arms: liraglutide 1.2 or 1.8 mg, placebo | 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 Parallel groups Sample size: 178/177 Primary endpoint: change in A1C FU duration: 26 weeks | | LEAD-5 (vs placebo), 2009 | Liraglutide 1.8 mg daily
(n=232) vs. Placebo on-top of sulphonylureas+metformin
(n=115)
| adult patients with type 2 diabetes
| double-blind Parallel groups Sample size: 232/115 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | LEAD-2 (Nauck) (1.2 mg vs glimepiride), 2009 | Liraglutide 1.2mg daily for 26 weeks (n=241) vs. Glimepiride on-top of Metformin (n=244) 5 arms: Liraglutide 0.6, 1.2 or 1.8 mg daily, glimepiride 4mg od, placebo | patients with type 3 diabetes previously treated with oral antidiabetes (OAD) therap | double blind Parallel groups Sample size: 241/244 Primary endpoint: change in A1C FU duration: 26 weeks | | LEAD-5 (vs Glargine), 2009 | Liraglutide 1.8 mg daily (n=232) vs. Glargine on-top of sulphonylureas+metformin (n=234) | adult patients with type 2 diabetes | open Parallel groups Sample size: 232/234 Primary endpoint: change in HbA1c FU duration: 26 weeks | | NN2211-1796 | liraglutide added to metformin (n=-9) vs. glimepiride added to metformin (n=-9) | | Sample size: -9/-9 Primary endpoint: Change in Glycosylated Haemoglobin A1c FU duration: | | LEAD-4 (1.8mg), 2009 | Liraglutide 1.8 daily
(n=178) vs. Placebo on-top of thiazolidinediones + metformin
(n=177) 3 arms: liraglutide 1.2 or 1.8 mg, placebo
| 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 Sample size: 178/177 Primary endpoint: change in A1C FU duration: 26 weeks
| | LEAD-1 SU (1.8 mg vs placebo), 2009 | Liraglutide 1.8 mg daily
(n=234) vs. Placebo on-top of sulphonylureas
(n=114) 5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo
| patients with type 2 diabetes
| double-blind Parallel groups Sample size: 234/114 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | LEAD-1 SU (1.8 vs rosiglitazone), 2009 | Liraglutide 0.6, 1.2 or 1.8 mg daily
(n=228) vs. rosiglitazone on-top of sulphonylureas
(n=232) 5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo
|
| double-blind Parallel groups Sample size: 228/232 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | LEAD-2 (Nauck) (1.8 mg vs glimepiride), 2009 | Liraglutide 1.8 mg daily for 26 weeks
(n=242) vs. Glimepiride on-top of Metformin
(n=244) 5 arms: Liraglutide 0.6, 1.2 or 1.8 mg daily,glimepiride or placebo
| patients with type 3 diabetes previously treated with oral antidiabetes (OAD) therap
| double blind Parallel groups Sample size: 242/244 Primary endpoint: change in A1C FU duration: 26 weeks
| | LEAD-2 (Nauck) (1.8mg vs placebo), 2009 | Liraglutide 1.8 mg daily
(n=242) vs. Placebo on-top of Metformin
(n=122) 5 arms : liraglutide 0.6, 1.2 or 1.8 mg, glimeripide 4mg once daily or placebo
| subjects previously treated with oral antidiabetes therapy
| double blind Parallel groups Sample size: 242/122 Primary endpoint: change in A1C FU duration: 26 weeks
| | Kaku 0.9mg, 2010 | liraglutide 0.9 mg/day
(n=88) vs. placebo
(n=88) 3 arms:liraglutide 0.6 mg/day, 0.9 mg/day or placebo
| Japanese patients with type 2 diabetes
| double-blind Sample size: 88/88 Primary endpoint: FU duration: 24 weeks
|
|
| diabetes type 2 | liraglutide | not classified | versus oral therapy No demonstrated result for efficacy liraglutide 1.2mg inferior to glimepiride in terms of nausea in LEAD-3 mono 1.2mg (Garber), 2009 liraglutide 1.2mg inferior to glimepiride in terms of vomiting in LEAD-3 mono 1.2mg (Garber), 2009 liraglutide 1.2mg inferior to glimepiride in terms of diarrhoea in LEAD-3 mono 1.2mg (Garber), 2009 liraglutide 1.2mg inferior to sitagliptin in terms of nausea in Pratley 1.2mg, 2010 liraglutide 1.8mg inferior to exenatide on top MET/SU/MET+SU in terms of severe adverse events in LEAD-6, 2009 liraglutide 1.8mg inferior to sitagliptin in terms of nausea in Pratley 1.8mg, 2010 liraglutide 1.8mg inferior to sitagliptin in terms of vomiting in Pratley 1.8mg, 2010 liraglutide 1.8mg inferior to sitagliptin in terms of diarrhoea in Pratley 1.8mg, 2010 liraglutide 1.8mg inferior to glimepiride in terms of nausea in LEAD-3 mono 1.8mg (Garber), 2009 liraglutide 1.8mg inferior to glimepiride in terms of vomiting in LEAD-3 mono 1.8mg (Garber), 2009 liraglutide 1.8mg inferior to glimepiride in terms of diarrhoea in LEAD-3 mono 1.8mg (Garber), 2009 | 12 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Madsbad (vs Glimepiride), 2004 | liraglutide other doses vs glimepiride | ant hypoglycemia 0.05 [0.01; 0.41] | | death NaN [NaN; NaN] CV events NaN [NaN; NaN] vomiting 0.58 [0.06; 5.34] diarrhoea ∞ [NaN; ∞] severe hypoglycemia NaN [NaN; NaN] | | Feinglos, 2005 | liraglutide other doses vs metformin | | | death NaN [NaN; NaN] CV events NaN [NaN; NaN] nausea 0.68 [0.15; 3.12] vomiting 0.77 [0.09; 6.70] severe hypoglycemia NaN [NaN; NaN] ant hypoglycemia 0.48 [0.10; 2.39] | | LEAD-3 mono 1.2mg (Garber), 2009 | liraglutide 1.2mg vs glimepiride | | nausea 3.25 [2.06; 5.12] vomiting 3.40 [1.65; 7.00] diarrhoea 1.75 [1.07; 2.87] | death 0.00 [0.00; NaN] severe hypoglycemia NaN [NaN; NaN] serious adverse events 1.22 [0.60; 2.47] | | Pratley 1.2mg, 2010 | liraglutide 1.2mg vs sitagliptin | | nausea 4.56 [2.36; 8.80] | death 0.00 [0.00; NaN] CV events 0.97 [0.06; 15.46] vomiting 1.87 [0.85; 4.11] diarrhoea 1.59 [0.74; 3.42] serious adverse events 1.49 [0.43; 5.19] severe adverse events 0.87 [0.32; 2.35] | | LEAD-6, 2009 | liraglutide 1.8mg vs exenatide on top MET/SU/MET+SU | | severe adverse events 2.80 [1.12; 6.97] | nausea 0.91 [0.67; 1.23] vomiting 0.60 [0.32; 1.14] diarrhoea 1.02 [0.63; 1.66] severe hypoglycemia 0.00 [0.00; NaN] serious adverse events 1.97 [0.75; 5.17] | | Seino, 2010 | liraglutide other doses vs glibenclamide | | | death ∞ [NaN; ∞] diarrhoea 1.67 [0.63; 4.44] severe hypoglycemia NaN [NaN; NaN] treatment-emergent
adverse events (TEAEs) 0.99 [0.87; 1.12] serious adverse events 0.80 [0.34; 1.88] severe adverse events 1.48 [0.30; 7.22] | | Pratley 1.8mg, 2010 | liraglutide 1.8mg vs sitagliptin | | nausea 5.93 [3.11; 11.28] vomiting 2.34 [1.10; 5.00] diarrhoea 2.51 [1.24; 5.10] | death 1.00 [0.06; 15.96] CV events 0.97 [0.06; 15.46] serious adverse events 1.51 [0.43; 5.27] severe adverse events 0.88 [0.32; 2.38] | | LEAD-3 mono 1.8mg (Garber), 2009 | liraglutide 1.8mg vs glimepiride | | nausea 3.84 [2.63; 5.59] vomiting 2.57 [1.21; 5.43] diarrhoea 2.10 [1.30; 3.38] | severe hypoglycemia NaN [NaN; NaN] serious adverse events 0.62 [0.26; 1.46] | | LEAD 1 (1.8 vs 1.2), 2009 | liraglutide 1.8mg vs liraglutide 1.2mg | | | | | LEAD 2 (1.8 vs 1.2), 2009 | liraglutide 1.8mg vs liraglutide 1.2mg | | | | | LEAD 4 (1.8 vs 1.2), 2009 | liraglutide 1.8mg vs liraglutide 1.2mg | | | | | LEAD-1 SU (1.2 vs rosiglitazone), 2009 | liraglutide 1.2mg vs rosiflitazone | | | |
| Trial | Treatments | Patients | Method |
|---|
| Madsbad (vs Glimepiride), 2004 | Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily (n=135) vs. Glimepiride (n=26) | Outpatients with type 2 diabetes | open Parallel groups Sample size: 135/26 Primary endpoint: change in HbA1c FU duration: 12 weeks dose-response study | | Feinglos, 2005 | Liraglutide 0.045, 0.225, 0.45, 0.6 or 0.75 mg daily for 12 weeks (n=176) vs. metformin 1000mg twice daily (n=34) | subjects with Type 2 diabetes | double blind (not adequate) Parallel groups Sample size: 176/34 Primary endpoint: not defiend FU duration: 12 weeks phase 2 dose response study | | LEAD-3 mono 1.2mg (Garber), 2009 | liraglutide 1.2 mg daily
(n=251) vs. glimepiride 8 mg once daily (n=248) 3 arms : liraglutide 1.2 or 1.8 mg daily or glimepiride 8 mg once daily | patients with early type 2 diabetes
| double blind Parallel groups Sample size: 251/248 Primary endpoint: Change in Glycosylated Haemoglobin A1c (HbA1c) , , FU duration: 52 weeks (104 weeks) phase 3
| | Pratley 1.2mg, 2010 | liraglutide 1.2mg subcutaneously once daily (n=225) vs. oral sitagliptin 100mg once daily (n=219) 2 dose of liraglutide 1.2 and 1.8 mg | patients with type 2 diabetes who did not have adequate glycemic control with metformin | open Parallel groups Sample size: 225/219 Primary endpoint: change in HbA1c FU duration: 26 weeks | | LEAD-6, 2009 | liraglutide 1.8 mg once a day (n=233) vs. exenatide 10 microg twice a day (n=231) | Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both | open Parallel groups Sample size: 233/231 Primary endpoint: change in glycosylated haemoglobin FU duration: 26 weeks | | Seino, 2010 | liraglutide 0.9 mg once daily (n=272) vs. glibenclamide once or twice daily at a planned maximum dose of 2.5 mg/day, before or after meals (n=139) | Japanese subjects with type 2 diabetes, inadequately controlled with diet therapy or oral antidiabetic drug monotherapy | double-blind Parallel groups Sample size: 272/139 Primary endpoint: HbA1c FU duration: 24-week | | Pratley 1.8mg, 2010 | liraglutide 1.8mg subcutaneously once daily
(n=221) vs. oral sitagliptin 100mg once daily
(n=219) 2 dose of liraglutide 1.2 and 1.8 mg
| patients with type 2 diabetes who did not have adequate glycemic control with metformin
| open Parallel groups Sample size: 221/219 Primary endpoint: change in HbA1c FU duration: 26 weeks
| | LEAD-3 mono 1.8mg (Garber), 2009 | liraglutide 1.8 mg daily
(n=247) vs. glimepiride 8 mg once daily
(n=248) 3 arms : liraglutide 1.2 or 1.8 mg daily or glimepiride 8 mg once daily
| subjects with type 2 diabetes
| double blind Parallel groups Sample size: 247/248 Primary endpoint: Change in Glycosylated Haemoglobin A1c (HbA1c) , , FU duration: 52 weeks (104 weeks) phase 3
| | LEAD 1 (1.8 vs 1.2), 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | LEAD 2 (1.8 vs 1.2), 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | LEAD 4 (1.8 vs 1.2), 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | LEAD-1 SU (1.2 vs rosiglitazone), 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | lixisenatide | not classified | versus add on insulin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| GETGOAL-L | lixisenatide vs placebo (add on basal insulin) | | | |
| Trial | Treatments | Patients | Method |
|---|
| GETGOAL-L | AVE0010 (10,15 and 20 µg) in association with basal insulin, with or without metformin (n=328) vs. placebo on top basal insulin (n=167) | Type 2 diabetes mellitus insufficiently controlled with basal insulin with or without metformin | double-blind Sample size: 328/167 Primary endpoint: change from baseline in HbA1c FU duration: 24 weeks |
|
| diabetes type 2 | lixisenatide | not classified | versus add on oral therapy No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Ratner DRI6012, 2010 | lixisenatide vs placebo (add on MET) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Ratner DRI6012, 2010 | subcutaneous lixisenatide doses of 5, 10, 20 or 30 microg once daily or twice daily (n=433) vs. placebo (n=109) | patients with Type 2 diabetes inadequately controlled with metformin (>= 1000 mg/day) | double-blind (nature not volume) Parallel groups Sample size: 433/109 Primary endpoint: change in HbA(1c) FU duration: 13 weeks dose–response study |
|
| diabetes type 2 | taspoglutide | not classified | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nauck 20 once weekly vs PBO, 2009 | taspoglutide 20mg once weekly vs placebo | | | | | Nauck 20 every 2 weeks vs PBO, 2009 | taspoglutide 20mg once every 2 weeks vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nauck 20 once weekly vs PBO, 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Nauck 20 every 2 weeks vs PBO, 2009 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | taspoglutide | not classified | versus add on oral therapy No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Ratner (20mg once weekly), 2010 | taspoglutide vs placebo (add on MET) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Ratner (20mg once weekly), 2010 | taspoglutide s.c. 20mg once weekly for 8 weeks (n=97) vs. placebo s.c. once
weekly on top metformin (n=32) 3 different regimens : 20 mg taspoglutide s.c. once weekly
for 4 weeks, followed by 4 weeks of 20 mg once weekly
(20/20), or titration up to 30 mg once-weekly (20/30) or
40 mg once-weekly (20/40) taspoglutide | subjects with Type 2 diabetes inadequately controlled on metformin alone | double-blind Parallel groups Sample size: 97/32 Primary endpoint: GI adverse events FU duration: 8 weeks (+4wk) phase 2 |
|
| diabetes type 2 | taspoglutide | not classified | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nauck 10 once weekly vs PBO, 2009 | taspoglutide 10mg once weekly vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nauck 10 once weekly vs PBO, 2009 | taspoglutide, either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks for 8 weeks (n=257) vs. placebo (n=49) | patients with type 2 diabetes inadequately controlled with metformin | double-blind Parallel groups Sample size: 257/49 Primary endpoint: change in A1C FU duration: 12 weeks phase 2b, dose ranging |
|
