| pathology | treatment | patient | Demonstrated benefit and harm | k | | | |
|---|
| diabetes type 2 | albiglutide | not classified | versus add on oral therapy No demonstrated result for efficacy | 1 trial | 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] |
| 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 |
|
| diabetes type 2 | alogliptin | not classified | versus placebo or control No demonstrated result for efficacy alogliptin inferior to placebo (add on MET) in terms of HbA1c goal <7% in Nauck, 2009 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nauck, 2009 | alogliptin vs placebo (add on MET) | | HbA1c goal <7% 2.40 [1.55; 3.70] | all hypoglycemia 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Nauck, 2009 | alogliptin 12.5 and 25 mg once daily (n=210) vs. placebo (n=104) | patients whose HbA(1c) levels were inadequately controlled on metformin alone | double-blind Parallel groups Sample size: 210/104 Primary endpoint: FU duration: 26 weeks |
|
| diabetes type 2 | dapagliflozin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Bailey (MB102014), 2010 | dapagliflozin vs placebo (add on MET) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Bailey (MB102014), 2010 | dapagliflozin (2¡¤5 mg, n=137; 5 mg, n=137; or 10 mg, n=135) (n=-9) vs. placebo (n=-9) | adults with type 2 diabetes who were receiving daily metformin (¡Ý1500 mg per day) and had inadequate glycaemic control | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: HbA1c FU duration: 24 weeks dose ranging |
|
| 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 No demonstrated result for efficacy | 2 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 | | | |
| 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 |
|
| 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 | 15 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] |
| 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
|
|
| 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 | 3 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) | | | |
| 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: |
|
| diabetes type 2 | glimeripide | not classified | versus placebo No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | Charpentier, 2001 | glimepiride vs placebo (add on MET) | | | CV death 1.00 [0.38; 2.62] All-cause mortality 1.00 [0.38; 2.62] Stroke 1.00 [0.38; 2.62] Myocardial infarction 1.00 [0.38; 2.62] | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Study 201 (Goldberg), 1996 | glimepiride, 1, 4, or 8 mg once daily (n=304) vs. placebo (n=0) | patients with NIDDM | double-blind Parallel groups Sample size: 304/0 Primary endpoint: FU duration: 14 weeks | | Schade, 1998 | glimepiride at individually determined optimal dose (1-8 mg of glimepiride) for 10+12 weeks (n=123) vs. placebo (n=126) | patients with type 2 diabetes mellitus for whom diet therapy is unsuccessful | double-blind Parallel groups Sample size: 123/126 Primary endpoint: FU duration: | | Rosenstock, 1996 | glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d (n=416) vs. placebo (n=0) | previously treated NIDDM patients | double-blind Parallel groups Sample size: 416/0 Primary endpoint: FU duration: 14 weeks | | Luis Bautista, 2003 | glimepiride with titration to 2 mg and 4 mg for FPG levels >120 mg/dL (n=-9) vs. placebo (n=-9) | Mexican American Patients with type 2 diabetes mellitus | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: change in HbA(1c) FU duration: 14 weeks | | Charpentier, 2001 | metformin and glimepiride (n=-9) vs. metformin (n=-9) metformin, glimepiride or metformin and glimepiride | Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily | double-blind Sample size: -9/-9 Primary endpoint: FU duration: | | Kaneko, 1993 | glimepiride 0.25mg od, 0.5mg od (n=62) vs. placebo (n=31) | | Sample size: 62/31 Primary endpoint: FU duration: | | Study 202 | glimepiride 1-8mg od (n=122) vs. placebo (n=125) | | Sample size: 122/125 Primary endpoint: FU duration: | | Riddle, 1994 | Glimepiride (16 mg/day) plus insulin (n=72) vs. insulin
plus placebo (n=73) | 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)) | Sample size: 72/73 Primary endpoint: FU duration: |
|
| diabetes type 2 | glimeripide | not classified | versus gliclazide No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Charpentier (301F) | glimepiride 1-4mg od (n=96) vs. gliclazide 80-320 mg/day (od or bid) (n=107) | | Sample size: 96/107 Primary endpoint: FU duration: |
|
| diabetes type 2 | glimeripide | not classified | versus Sulfonylurea No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Draeger, 1996 | glimepiride 1 mg daily (n=524) vs. 2.5 mg glibenclamide (n=520) | type 2 diabetic patients stabilised on glibenclamide | double-blind Parallel groups Sample size: 524/520 Primary endpoint: not unique FU duration: | | Dills, 1996 | glimepiride 1-16mg od (n=289) vs. non-micronized glyburide 1.25-20mg od (n=288) | patients with non-insulin dependent diabetes | double-blind Parallel groups Sample size: 289/288 Primary endpoint: FU duration: | | Inukai, 2005 | glimepiride (n=172) vs. gliclazide or glibenclamide (n=0) | Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU | open Parallel groups Sample size: 172/0 Primary endpoint: FU duration: 6 months | | Protocol 311 | glimepiride 1-8mg od (n=427) vs. glibenclamide 1.75-14 mg/day
(od or bid) (n=425) | | Sample size: 427/425 Primary endpoint: FU duration: | | Clark (301), 1997 | glimepiride 1-16 mg/day (od or bid) (n=444) vs. glipizide 2.5-40 mg/day (od or bid) (n=208) | | Sample size: 444/208 Primary endpoint: FU duration: | | Sonnenberg, 1997 | glimepirid e6mg od (n=50) vs. glimepiride 3mg bid (n=48) | | Cross over Sample size: 50/48 Primary endpoint: FU duration: |
|
| diabetes type 2 | glipizide | not classified | versus No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Rosenstock, 1993 | glipizide, 2.5 or 5 mg/day (n=139) vs. glyburide, 1.25 or 2.5 mg/day (n=0) | elderly patients with NIDDM that was controlled for at least 3 months with oral sulfonylurea therapy | open Parallel groups Sample size: 139/0 Primary endpoint: FU duration: 4 months | | Birkeland, 1994 | glipizide (n=-9) vs. glyburide (n=-9) | NIDDM patients | Sample size: -9/-9 Primary endpoint: FU duration: | | Birkeland, 1994 | glipizide (n=-9) vs. glyburide (n=-9) | NIDDM patients | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 15 months | | Simonson, 1997 | once-daily doses of 5, 20, 40, or 60 mg glipizide GITS (n=-9) vs. placebo (n=-9) | NIDDM patients | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 4+8 weeks | | Testa, 1998 | 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n=377) vs. placebo (n=192) | patients with type 2 diabetes mellitus | Parallel groups Sample size: 377/192 Primary endpoint: FU duration: 12 weeks | | Goldstein | glipizide/metformin 5/500 mg tablets (n=-9) vs. metformin 500-mg (n=-9) glipizide 30-mg, metformin 500-mg, or glipizide/metformin 5/500 mg | patients with type 2 DM that is uncontrolled by at least half the maximum labeled daily dose of a sulfonylurea | open Cross over Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | glyburide | not classified | versus No demonstrated result for efficacy | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Garber, 2002 | glyburide 2.5 mg (n=-9) vs. placebo (n=-9) | patients with type 2 diabetes who had failed diet and exercise | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Vray, 1995 | glibenclamide (2.5 mg X 3/d) (n=-9) vs. placebo (n=-9) | type 2 diabetic outpatients, 40-70 years of age, treated by diet alone or oral anti-diabetic drugs | double-blind Factorial plan Sample size: -9/-9 Primary endpoint: FU duration: | | Hermann, 1991 | metformin + glibenclamide (n=-9) vs. metformin (n=-9) metformin, glibenclamide or the combination of both | patients with non-insulin-dependent diabetes mellitus | Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 6 months | | DeFronzo, 1995 | metformin and glyburide (n=-9) vs. metformin (n=-9) metformin and glyburide vs. metformin vs. glyburide | patients with non-insulin-dependent diabetes mellitus | double-blind Sample size: -9/-9 Primary endpoint: FU duration: 29 weeks | | Erle, 1999 | low-dose glyburide plus metformin (n=-9) vs. high-dose glyburide alone (n=-9) | | Cross over Sample size: -9/-9 Primary endpoint: FU duration: | | 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 (n=-9) vs. metformin 500 mg, (n=-9) metformin 500 mg, glibenclamide 5 mg, metformin-glibenclamide 500 mg/2.5 mg or metformin-glibenclamide 500 mg/5 mg | patients with Type 2 diabetes mellitus inadequately controlled by metformin monotherapy | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 16 weeks | | Blonde, 2002 | glyburide/metformin 2.5 mg/500 mg (n = 160); or glyburide/metformin 5 mg/500 mg (n = 162) (n=-9) vs. metformin 500 mg (n=-9) glyburide 10 mg b.i.d. (n = 164); metformin 500 mg (n = 153); glyburide/metformin 2.5 mg/500 mg (n = 160); or glyburide/metformin 5 mg/500 mg | patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 16 weeks | | Tosi, 2003 | metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d (n=-9) vs. metformin (500 to 3,000 mg/d), (n=-9) metformin (500 to 3,000 mg/d), glibenclamide (5 to 15 mg/d), or their combination (metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d | | double-blind Cross over Sample size: -9/-9 Primary endpoint: FU duration: 6 months | | Garber, 2003 | glyburide/metformin (n=-9) vs. metformin (n=-9) glyburide/metformin tablets vs. metformin or glyburide monotherapy | patients with type 2 diabetes who had inadequate glycemic control [glycosylated hemoglobin A(1C) (A1C), >7% and <12%) with diet and exercise alone | Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | linagliptin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Owens | linagliptin vs Metformin + sulfonylurea | | | |
| Trial | Treatments | Patients | Method |
|---|
| Owens | linagliptin
(n=-9) vs. combination of metformin and an SU
(n=-9)
| type 2 diabetes mellitus with insufficient glycaemic control with metformin in combination with a sulphonylurea
| Sample size: -9/-9 Primary endpoint: change from baseline in HbA1c FU duration: 24 weeks
|
|
| diabetes type 2 | linagliptin | not classified | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Lewin, 2010 | linagliptin vs placebo (add on SU) | | | | | Del Prato | linagliptin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Lewin, 2010 | linagliptin 5 mg
(n=-9) vs. placebo (add-on to sulphonylurea)
(n=-9)
| patients with type 2 diabetes and insufficient glycaemic control
| double-blind Sample size: -9/-9 Primary endpoint: change from baseline HbA1c FU duration: 18 weeks
| | Del Prato | Linagliptin monotherapy
(n=-9) vs. placebo
(n=-9)
| Type 2 Diabetic Patients With Insufficient Glycemic Control
| double-blind Sample size: -9/-9 Primary endpoint: change from baseline in HbA1c FU duration: 24 weeks
|
|
| diabetes type 2 | linagliptin | not classified | versus SU No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Gallwitz, 2012 | linagliptin vs glimepiride (add on MET) | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gallwitz, 2012 | linagliptin (5 mg once daily) add-on therapy to preferably > 1500 mg metformin (n=777) vs. glimepiride (1—4 mg) orally once daily add-on therapy to preferably > 1500 mg metformin (n=775) | type 2 diabetes mellitus with insufficient glycaemic control with metformin | double-blind Parallel groups Sample size: 777/775 Primary endpoint: change from baseline in HbA1c FU duration: 104 weeks |
|
| diabetes type 2 | liraglutide | not classified | versus add on oral therapy No demonstrated result for efficacy 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 | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| 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-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] | | | 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) | | | |
| Trial | Treatments | Patients | Method |
|---|
| 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-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 | | 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
|
|
| diabetes type 2 | liraglutide | not classified | versus oral therapy No demonstrated result for efficacy 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 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| 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] |
| Trial | Treatments | Patients | Method |
|---|
| 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
|
|
| 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 | mitiglinide | not classified | versus No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gao | mitiglinide 10 - 20 mg three times daily (n=291) vs. nateglinide 120 mg three times daily (n=0) | Chinese type 2 diabetes mellitus patients | double-blind Parallel groups Sample size: 291/0 Primary endpoint: FU duration: 20 weeks | | Kaku, 2009 | additional mitiglinide 5 or 10 mg tid (n=-9) vs. placebo on top pioglitazone (n=-9) | Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapy | multicenter Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 16 weeks | | Kumashiro, 2007 | mitiglinide (n=-9) vs. on top of once daily insulin glargine (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | nateglinide | not classified | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Li, 2009 | Nateglinide (n=-9) vs. repaglinide (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Li, 2007 | nateglinide 90 mg three times daily (n=115) vs. repaglinide 1.0 mg three times daily (n=115) | Chinese patients with type 2 diabetes | Parallel groups Sample size: 115/115 Primary endpoint: FU duration: 12 weeks |
|
| diabetes type 2 | nateglinide | not classified | versus placebo or control No demonstrated result for efficacy | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Marre, 2002 | nateglinide 60 mg, 120 mg before three meals (n=-9) vs. placebo (n=-9) | metformin-treated patients with HbA1c between 6.8% and 11% | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Horton, 2000 | 120 mg nateglinide before meals (n=179) vs. placebo (n=172) | patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in | double-blind Parallel groups Sample size: 179/172 Primary endpoint: FU duration: | | Hanefeld, 1990 | nateglinide at doses of 30 mg, 60 mg, 120 mg, or 180 mg (n=229) vs. placebo (n=60) | | double-blind Parallel groups Sample size: 229/60 Primary endpoint: FU duration: 12 weeks | | Saloranta, 2002 | nateglinide (30, 60, or 120 mg, with meals). (n=675) vs. placebo (n=0) | patients with type 2 diabetes but only moderately elevated fasting plasma glucose (FPG = 7.0-8.3 mmol/liter) | double-blind Parallel groups Sample size: 675/0 Primary endpoint: FU duration: 24 weeks | | Mari, 2005 | 30, 60, or 120 mg nateglinide (n=108) vs. placebo (n=0) | mild type 2 diabetic men and women (fasting glucose 7.0-8.3 mmol/l) on diet treatment | double_blind Parallel groups Sample size: 108/0 Primary endpoint: FU duration: 24 weeks | | Goldberg, 1998 | repaglinide (n=66) vs. placebo (n=33) | type 2 diabetes | double-blind Parallel groups Sample size: 66/33 Primary endpoint: FU duration: | | Jovanovic, 2000 | repaglinide 1 mg or repaglinide 4 mg (n=286) vs. placebo (n=75) | | double-blind Parallel groups Sample size: 286/75 Primary endpoint: FU duration: 24 weeks | | 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. (n=253) vs. placebo (n=0) | pharmacotherapy-naive patients with Type 2 diabetes | double-blind Parallel groups Sample size: 253/0 Primary endpoint: FU duration: 16 weeks | | Moses, 2001 | 0.5 mg repaglinide at mealtimes (increased to 1 mg after 4 weeks depending on blood glucose response) (n=408) vs. placebo (n=0) | patients with type 2 diabetes considered poorly controlled by diet, but without a history of previous antidiabetic medication | double-blind Parallel groups Sample size: 408/0 Primary endpoint: FU duration: 16 weeks |
|
| diabetes type 2 | nateglinide | not classified | versus active treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Ristic, 2006 | nateglinide plus metformin (n=133) vs. gliclazide plus metformin (n=129) | Patients with inadequate glucose control on maximal doses of metformin | double-blind Parallel groups Sample size: 133/129 Primary endpoint: FU duration: 24 weeks |
|
| diabetes type 2 | pioglitazone | not classified | versus standard glucose-lowering drugs No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PNFP-014 | pioglitazone + insulin vs placebo (add on insulin) | | | death NaN [NaN; NaN] serious heart failure ∞ [NaN; ∞] stroke NaN [NaN; NaN] myocardial infarction ∞ [NaN; ∞] Death, Myocardial infarction, stroke ∞ [NaN; ∞] | | OPI-502 | pioglitazone + insulin vs placebo (add on insulin) | | | death NaN [NaN; NaN] serious heart failure NaN [NaN; NaN] stroke NaN [NaN; NaN] myocardial infarction 0.00 [0.00; NaN] Death, Myocardial infarction, stroke 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| PNFP-014 | Pioglitazone insulin (n=379) vs. Placebo + insulin (n=187) | patients with type 2 diabetes | Parallel groups Sample size: 379/187 Primary endpoint: FU duration: 16 wk | | OPI-502 | Pioglitazone + insulin (n=110) vs. Placebo + insulin (n=112) | Insulin-dependent DM-2 | Parallel groups Sample size: 110/112 Primary endpoint: FU duration: 20 wk |
|
| diabetes type 2 | repaglinide | not classified | versus No demonstrated result for efficacy | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Lund, 2007 | repaglinide 2 mg thrice daily (n=-9) vs. metformin 1 g twice daily (n=-9) | non-obese patients with type 2 diabetes | double-blind Cross over Sample size: -9/-9 Primary endpoint: FU duration: | | Landgraf, 1999 | repaglinide, administered preprandially three times daily (n=-9) vs. glibenclamide, given preprandially once or twice daily (n=-9) | | double-blind Sample size: -9/-9 Primary endpoint: FU duration: 14 weeks | | Marbury, 1999 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Wolffenbuttel, 1999 | repaglinide (0.5-4 mg t.i.d.) (n=211) vs. glyburide (1.75-10.5 mg daily) (n=109) | | double-blind Sample size: 211/109 Primary endpoint: FU duration: 1 year | | Madsbad, 2001 | repaglinide, 1-4 mg at mealtimes (n=256) vs. glipizide, 5-15 mg daily (n=0) | | double-blind Sample size: 256/0 Primary endpoint: FU duration: 1 year | | Raskin, 2000 | repaglinide (0.5–4.0 mg at meals), (n=256) vs. combination of repaglinide (1–4 mg at meals) and troglitazone (200–600 mg once
daily) (n=0) | Patients with type 2 diabetes who
had inadequate glycemic control (HbA1c 7.0%) during previous monotherapy | open Sample size: 256/0 Primary endpoint: FU duration: 22 weeks | | Raskin, 2001 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Raskin, 2001 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Landin-Olsson, 1999 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | repaglinide | not classified | versus placebo or control No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Moses, 1999 | prestudy dose of metformin with the addition of repaglinide (n=27) vs. prestudy dose of metformin (n=27) | patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin | open Parallel groups Sample size: 27/27 Primary endpoint: FU duration: 12 weeks | | Chuang, 1999 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Goldberg, 1998 | repaglinide (n=66) vs. placebo (n=33) | patients with type 2 diabetes | double-blind Parallel groups Sample size: 66/33 Primary endpoint: FU duration: 18 weeks | | Jovanovic, 2000 | repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146) (n=286) vs. placebo (n=75) | | double-blind Sample size: 286/75 Primary endpoint: FU duration: 24 weeks |
|
| diabetes type 2 | rosiglitazone | not classified | versus standard glucose-lowering drugs No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BRL 49653/347 | rosiglitazone vs placebo (add on insulin) | | | | | 49653/085 | rosiglitazone vs placebo (add on insulin) | | | | | 49653/095 | rosiglitazone vs placebo (add on insulin) | | | | | 49653/136 | rosiglitazone vs placebo | | | | | SB-712753/009 | rosiglitazone vs | | | |
| Trial | Treatments | Patients | Method |
|---|
| BRL 49653/347 | Rosiglitazone and insulin (n=418) vs. Insulin (n=212) | patients with type 2 diabetes poorly controlled on insulin | Parallel groups Sample size: 418/212 Primary endpoint: FU duration: 24 wk | | 49653/085 | Rosiglitazone and insulin (n=138) vs. Insulin (n=139) | patients with type 2 diabetes | Parallel groups Sample size: 138/139 Primary endpoint: FU duration: 26 wk | | 49653/095 | Rosiglitazone and insulin (n=196) vs. Insulin (n=96) | patients with type 2 diabetes poorly controlled on insulin | Parallel groups Sample size: 196/96 Primary endpoint: FU duration: 26 wk | | 49653/136 | Rosiglitazone (n=148) vs. Placebo (n=143) | patients with type 2 diabetes and chronic renal failure on Su, insulin, or both | Parallel groups Sample size: 148/143 Primary endpoint: FU duration: 26 wk | | SB-712753/009 | Rosiglitazone, metformin, and insulin (n=162) vs. Insulin (n=160) | patients with type 2 diabetes with insulin | Parallel groups Sample size: 162/160 Primary endpoint: FU duration: 24 wk |
|
| diabetes type 2 | saxagliptin | not classified | versus placebo or control No demonstrated result for efficacy saxagliptin inferior to placebo (add on MET) in terms of HbA1c goal <7% in DeFronzo, 2009 | 11 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| DeFronzo, 2009 | saxagliptin vs placebo (add on MET) | | HbA1c goal <7% 2.63 [1.81; 3.81] | all hypoglycemia 0.94 [0.06; 14.87] | | saxgliptin, renal study | saxagliptin vs placebo (add on current treatment) | | | | | Rosenstock, 2008 | saxagliptin vs placebo (monotherapy) | | | | | CV181-011 | saxagliptin vs placebo (monotherapy) | | | | | CV181-038 | saxagliptin vs placebo (monotherapy) | | | | | Jadzinsky, 2009 | saxagliptin vs placebo (add on MET) | | | | | CV181-057 | saxagliptin vs placebo (add on insulin) | | | | | CV181-066 | saxagliptin vs placebo (add on MET) | | | | | CV181-080 | saxagliptin vs placebo (add on MET) | | | | | Hollander | saxagliptin vs placebo (add on TZD) | | | | | CV181-041 | saxagliptin vs placebo (monotherapy) | | | |
| Trial | Treatments | Patients | Method |
|---|
| DeFronzo, 2009 | saxagliptin (2.5, 5, or 10 mg once daily) (n=191) vs. placebo (n=179) | Patients With Inadequately Controlled
Type 2 Diabetes With Metformin Alone | Sample size: 191/179 Primary endpoint: FU duration: 24 weeks | | saxgliptin, renal study | saxagliptin (n=-9) vs. placebo added to patients’ current diabetes treatment (n=-9) | patients with moderate to severe renal impairment or end-stage renal disease | Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 12 weeks | | Rosenstock, 2008 | saxagliptin 2.5, 5, 10, 20 or 40 mg once daily (n=-9) vs. placebo (n=-9) | drug-naive patients with T2DM and inadequate glycaemic control | Sample size: -9/-9 Primary endpoint: FU duration: 12 weeks | | CV181-011 | oral saxagliptin 2.5, 5, or 10 mg once daily (n=-9) vs. placebo (n=-9) treatment-naïve patients with type 2 diabetes | | Sample size: -9/-9 Primary endpoint: FU duration: 24 weeks | | CV181-038 | Saxagliptin monotherapy (n=-9) vs. placebo (n=-9) | type 2 diabetic subjects who are not controlled with diet and exercise | Sample size: -9/-9 Primary endpoint: FU duration: | | Jadzinsky, 2009 | saxagliptin (n=-9) vs. placebo (n=-9) | treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control | Sample size: -9/-9 Primary endpoint: FU duration: | | CV181-057 | Saxagliptin, 5 mg (n=-9) vs. placebo (on top insulin) (n=-9) | Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin | Sample size: -9/-9 Primary endpoint: FU duration: | | CV181-066 | Saxagliptin (n=-9) vs. placebo (n=-9) | Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet And Exercise And A Stable Dose Of Metformin ¡Ý1500 mg/Day | Sample size: -9/-9 Primary endpoint: FU duration: | | CV181-080 | 2.5 mg Saxagliptin, Twice Daily (n=-9) vs. placebo (n=-9) | Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone | Sample size: -9/-9 Primary endpoint: FU duration: | | Hollander | saxagliptin (2.5 or 5 mg) (n=-9) vs. placebo (n=-9) | patients with type 2 diabetes and inadequate control on thiazolidinedione alone | Sample size: -9/-9 Primary endpoint: FU duration: | | CV181-041 | Saxagliptin (n=-9) vs. placebo (n=-9) | Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| diabetes type 2 | saxagliptin | not classified | versus SU No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| saxagliptin vs sitagliptin | saxagliptin vs sitagliptin (add on MET) | | | |
| Trial | Treatments | Patients | Method |
|---|
| saxagliptin vs sitagliptin | saxagliptin 5 mg once daily add on metformin (n=403) vs. sitagliptin 100 mg onece daily add on metformin (n=398) | adults with type 2 diabetes who did not attain adequate glycemic control on metformin therapy alone | Parallel groups Sample size: 403/398 Primary endpoint: FU duration: 18 weeks |
|
| diabetes type 2 | sitagliptin | not classified | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Charbonnel, 2006 | sitagliptin vs placebo (add on MET) | | | Adverse events leading to treatment discontinuation 1.34 [0.60; 2.98] | | Hermansen, 2007 | sitagliptin vs placebo (on-top glimepiride+/- metformine) | | | Adverse events leading to treatment discontinuation 2.74 [0.29; 25.95] | | Nauck, 2007 | sitagliptin vs placebo (add on MET) | | | Adverse events leading to treatment discontinuation 0.76 [0.40; 1.44] | | Rosenstock (sit on top pio vs pbo), 2006 | sitagliptin vs placebo (on top PIO) | Adverse events leading to treatment discontinuation 5.59 [1.26; 24.88] | | | | Scott** (sit vs pbo on top met), 2007 | sitagliptin vs placebo (add on MET) | | | Adverse events leading to treatment discontinuation 3.87 [0.44; 33.99] |
| Trial | Treatments | Patients | Method |
|---|
| Charbonnel, 2006 | sitagliptin 100 mg daily (add-on to metformin therapy)j (n=-9) vs. placebo (add-on tometformin therapy); (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Hermansen, 2007 | sitagliptin 100 mg daily (add-on to ongoing stable doses of glimepiride, alone or in combination with metformin)ocumen (n=-9) vs. placebo (add-on to ongoing stable doses of glimepiride, alone or in combination with metformin); (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Nauck, 2007 | sitagliptin 100 mg daily (add-on to metformin therapy)j (n=-9) vs. placebo (add-on to metformin therapy); (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Rosenstock (sit on top pio vs pbo), 2006 | sitagliptin 100 mg daily (add-on to pioglitazone therapy)sl˜ðõØ (n=-9) vs. placebo (add-on to pioglitazone therapy); (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: | | Scott** (sit vs pbo on top met), 2007 | sitagliptin 100 mg daily (add-on to metformin therapy)j (n=-9) vs. placebo (add-on to metformin therapy). (n=-9) | patients with type 2 diabetes who were inadequately on mET monotherapy | 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 |
|
| diabetes type 2 | vildagliptin | not classified | versus placebo or control No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Ahren, 2004 | vildagliptin vs placebo (add on MET) | | | Adverse events leading to treatment discontinuation NaN [NaN; NaN] | | Bosi, 2007 | vildagliptin vs placebo (add on MET) | | | Adverse events leading to treatment discontinuation 1.73 [0.52; 5.81] | | Fonseca, 2007 | vildagliptin vs placebo (add on insulin) | Adverse events leading to treatment discontinuation 9.50 [1.22; 74.05] | | | | Garber, 2007 | vildagliptin vs placebo (on top pioglitazone) | | | Adverse events leading to treatment discontinuation 1.25 [0.34; 4.57] | | Goodman, 2009 | vildagliptin vs placebo (add on MET) | | | all hypoglycemia ∞ [NaN; ∞] |
| Trial | Treatments | Patients | Method |
|---|
| Ahren, 2004 | vildagliptin 50 mg daily (add-on to metformin therapy)j (n=56) vs. placebo (add-on to metformin therapy)mag (n=51) | patients with type 2 diabetes | double-blind Sample size: 56/51 Primary endpoint: FU duration: 12 weeks | | Bosi, 2007 | vildagliptin (50 or) 100 mg daily (add-on to metformin therapy)m (n=185) vs. placebo (add-on to metformin therapy)mag (n=182) | patients with type 2 diabetes inadequately controlled with metformin | double-blind Sample size: 185/182 Primary endpoint: FU duration: | | Fonseca, 2007 | vildagliptin 100 mg daily (add-on to insulin therapy)y) (n=144) vs. placebo (add-on to insulin therapy)y)mag (n=152) | type 2 diabetes that was inadequately controlled by insulin | double-blind Sample size: 144/152 Primary endpoint: FU duration: 24 weeks | | Garber, 2007 | vildagliptin 50 or 100 mg daily (add-on to pioglitazone therapy) (n=463) vs. placebo (add-on to pioglitazone therapy) (n=0) | | Sample size: 463/0 Primary endpoint: FU duration: | | Goodman, 2009 | ildagliptin 100 mg given in the morning, vildagliptin 100 mg given in the evening (n=125) vs. placebo (n=122) | patients inadequately controlled with metformin | double-blind Parallel groups Sample size: 125/122 Primary endpoint: FU duration: 24 weeks |
|
| diabetes type 2 | vildagliptin | not classified | versus SU No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Ferrannini, 2009 | vildagliptin vs Sulfonylurea (add on to MET) | all hypoglycemia 0.10 [0.07; 0.16] | | HbA1c goal <7% 0.97 [0.90; 1.05] |
| Trial | Treatments | Patients | Method |
|---|
| Ferrannini, 2009 | vildagliptin 50 mg twice daily (n=1396) vs. glimepiride titrated up to 6 mg/day (n=1393) | Patients inadequately controlled on metformin monotherapy (HbA(1c) 6.5-8.5%) | double-blind Parallel groups Sample size: 1396/1393 Primary endpoint: HbA1c FU duration: 52 weeks |
|
| diabetes type 2 | vildagliptin | not classified | versus TZD No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Bolli, 2008 | vildagliptin vs pioglitazone (add on MET) | | | Adverse events leading to treatment discontinuation 0.95 [0.38; 2.36] | | Rosenstock** (vilda + pio vs pio), 2007 | vildagliptin vs placebo (add on TZD) | | | Adverse events leading to treatment discontinuation 0.47 [0.15; 1.49] |
| Trial | Treatments | Patients | Method |
|---|
| Bolli, 2008 | vildagliptin 100 mg daily (add-on to metformin therapy) (n=295) vs. pioglitazone 30 mg daily (add-on to metformin therapy)j (n=281) | patients with type 2 diabetes inadequately controlled with metformin monotherapy | double-blind Sample size: 295/281 Primary endpoint: FU duration: | | Rosenstock** (vilda + pio vs pio), 2007 | vildagliptin 50 mg or 100 mg daily plus 15 mg or 30 mg pioglitazone dailyi (n=-9) vs. pioglitazone 30 mg daily (n=-9) | drug-naive patients with type 2 diabetes | double-blind Sample size: -9/-9 Primary endpoint: FU duration: 24 weeks |
|
