| mechanism | treatment | Demonstrated benefit and harm | k | | | |
|---|
| cannabinoid-1 receptor blocker | rimonabant | versus placebo or control No demonstrated result for efficacy rimonabant 20mg inferior to placebo in terms of serious psychiatric side-effects in Rio-lipid 20 mg, 2005 rimonabant inferior to placebo in terms of serious psychiatric side-effects in CRESCENDO, 2010 | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RIO europe 20mg, 2005 | rimonabant 20mg vs placebo | weight loss equal to or greater than 10 percent 3.80 [2.49; 5.80] weight loss equal to or greater than 5 percent 2.68 [2.10; 3.42] | | serious psychiatric side-effects 1.24 [0.58; 2.67] serious adverse events 1.15 [0.72; 1.84] | | Rio-lipid 20 mg, 2005 | rimonabant 20mg vs placebo | weight loss equal to or greater than 10 percent 4.47 [2.98; 6.71] | serious psychiatric side-effects 6.92 [1.58; 30.22] | serious adverse events 1.73 [0.74; 4.07] | | RIO-North America 20 mg, 2006 | rimonabant 20mg vs placebo | weight loss equal to or greater than 10 percent 2.94 [2.23; 3.88] weight loss equal to or greater than 5 percent 2.44 [2.06; 2.89] | | serious psychiatric side-effects 1.68 [0.77; 3.68] serious adverse events 1.30 [0.80; 2.14] | | RIO europe 5mg, 2005 | rimonabant 5mg vs placebo | | | | | CRESCENDO, 2010 | rimonabant vs placebo | | serious psychiatric side-effects 1.92 [1.54; 2.39] | CV events 0.96 [0.84; 1.11] suicide 3.97 [0.44; 35.53] |
| Trial | Treatments | Patients | Method |
|---|
| RIO europe 20mg, 2005 | rimonabant 20mg daily (n=599) vs. placebo (n=305) | patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or bothtž-dt | Double blind Parallel groups Sample size: 599/305 Primary endpoint: weight change from baseline after 1 year of treatment FU duration: | | Rio-lipid 20 mg, 2005 | rimonabant 20 mg daily (n=346) vs. placebo (n=342) this was a 3-arms trial testing also rimonabant 5mg daily | overweight or obese patients (body-mass index 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) | Double blind Parallel groups Sample size: 346/342 Primary endpoint: loss of body weight FU duration: 12 months | | RIO-North America 20 mg, 2006 | rimonabant 20mg daily (n=1222) vs. placebo (n=607) | obese (body mass index >=30) or overweight (body mass index >=27 and treated or untreated hypertension or dyslipidemia) adult patients | Double blind Parallel groups Sample size: 1222/607 Primary endpoint: Body weight change over year 1ú FU duration: | | RIO europe 5mg, 2005 | 5 mg rimonabant (n=603) vs. placebo (n=305) 3 arms: placebo, 5 mg rimonabant, or 20 mg rimonabant once daily | patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or both | double-blind Parallel groups Sample size: 603/305 Primary endpoint: weight FU duration: 1 y | | CRESCENDO, 2010 | rimonabant 20 mg (n=9381) vs. placebo (n=9314) | patients patients with abdominal obesity and with previously manifest or increased risk of vascular disease | double-blind Parallel groups Sample size: 9381/9314 Primary endpoint: CV death, MI, stroke FU duration: 13.8 months the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant |
|
| cannabinoid-1 receptor blocker | rimonabant | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RIO europe (20 vs 5 mg), 2005 | rimonabant 20mg vs rimonabant 5mg | | | |
| Trial | Treatments | Patients | Method |
|---|
| RIO europe (20 vs 5 mg), 2005 | (n=599) vs. (n=603) | | Sample size: 599/603 Primary endpoint: FU duration: |
|
| weight-loss drugs | Bupropion | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Anderson, 2002 | Bupropion vs placebo | | | | | Croft, 2002 | Bupropion vs placebo | | | | | Jain, 2002 | Bupropion vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Anderson, 2002 | bupropion SR 300, or 400 mg/d. (n=105) vs. placebo (n=112) | obese adults | double-blind Sample size: 105/112 Primary endpoint: FU duration: 24 weeks | | Croft, 2002 | Bupropion, 300 mg for 44 wk (n=210) vs. Placebo (n=213) | patients with major depression responder to open-label treatment with bupropion SR | double-blind Sample size: 210/213 Primary endpoint: FU duration: 44 weeks | | Jain, 2002 | bupropion SR 300 mg/d (n=213) vs. Placebo (n=209) | Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) | double-blind Sample size: 213/209 Primary endpoint: FU duration: 26 weeks |
|
| weight-loss drugs | liraglutide | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Astrup (NN8022-1807 ), 2009 | liraglutide vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Astrup (NN8022-1807 ), 2009 | 4 liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg daily) (n=-9) vs. placebo (n=-9) 3rd arms with orlistat 120 mg three times a day orally (n = 95) | obese individuals without type 2 diabetes | double blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 20 weeks |
|
| weight-loss drugs | lorcaserin | versus placebo or control No demonstrated result for efficacy lorcaserin inferior to placebo in terms of 10% Weight Loss Responders in BLOSSOM (10mg bid), 2009 lorcaserin inferior to placebo in terms of 5% Weight Loss Responders in BLOSSOM (10mg bid), 2009 lorcaserin inferior to placebo in terms of 10% Weight Loss Responders in BLOOM, 2010 lorcaserin inferior to placebo in terms of 5% Weight Loss Responders in BLOOM, 2010 lorcaserin inferior to placebo in terms of 10% Weight Loss Responders in BLOOM-DM (10mg bid) lorcaserin inferior to placebo in terms of 5% Weight Loss Responders in BLOOM-DM (10mg bid) | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BLOSSOM (10mg bid), 2009 | lorcaserin vs placebo | | 10% Weight Loss Responders 2.32 [1.94; 2.77] 5% Weight Loss Responders 1.89 [1.71; 2.09] | | | BLOOM, 2010 | lorcaserin vs placebo | | 10% Weight Loss Responders 2.94 [2.41; 3.59] 5% Weight Loss Responders 2.34 [2.09; 2.62] | | | BLOOM-DM (10mg bid) | lorcaserin vs placebo | | 10% Weight Loss Responders 3.68 [1.94; 7.00] 5% Weight Loss Responders 2.32 [1.68; 3.22] | |
| Trial | Treatments | Patients | Method |
|---|
| BLOSSOM (10mg bid), 2009 | lorcaserin 10 mg twice daily (n=1603) vs. placebo (n=1603) 3 arms trial with lorcaserin 10 mg twice daily, 10 mg once daily, and placebo | obese and overweight patients | double blind Parallel groups Sample size: 1603/1603 Primary endpoint: hierarchical testing procedure FU duration: 1 year | | BLOOM, 2010 | lorcaserin 10mg bid (n=-9) vs. placebo (n=-9) | | double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 52 weeks | | BLOOM-DM (10mg bid) | lorcaserin 10 mg BID (n=253) vs. placebo (n=56) the lorcaserin 10mg QD was interrupted prematurely due to slow enrollment | overweight and obese patients with type 2 diabetes mellitus managed with oral hypoglycemic agents | double-blind Parallel groups Sample size: 253/56 Primary endpoint: FU duration: 52 weeks |
|
| weight-loss drugs | orlistat | versus placebo or control No demonstrated result for efficacy | 28 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Bakris, 2002 | Orlistat vs placebo | | | | | Broom, 2002 | Orlistat vs placebo | | | | | Broom,, 2001 | Orlistat vs placebo | | | | | Davidson, 1999 | Orlistat vs placebo | | | | | Deerochanawong,, 2001 | Orlistat vs placebo | | | | | Derosa, 2003 | Orlistat vs placebo | | | | | Gotfredsen, 2001 | Orlistat vs placebo | | | | | Halpern, 2003 | Orlistat vs placebo | | | | | Hanefeld, 2002 | Orlistat vs placebo | | | | | Hauptman, 2000 | Orlistat vs placebo | | | | | Hill, 1999 | Orlistat vs placebo | | | | | Hollander, 1998 | Orlistat vs placebo | | | | | Karhunen, 2000 | Orlistat vs placebo | | | | | Kelley, 2002 | Orlistat vs placebo | | | | | Krempf, 2005 | Orlistat vs placebo | | | | | Lindgarde, 2000 | Orlistat vs placebo | | | | | Lucas, 2003 | Orlistat vs placebo | | | | | Micic, 1999 | Orlistat vs placebo | | | | | Miles, 2002 | Orlistat vs placebo | | | | | Muls, 2001 | Orlistat vs placebo | | | | | Naumov, 2002 | Orlistat vs placebo | | | | | Reaven, 2001 | Orlistat vs placebo | | | | | Rissanen, 2001 | Orlistat vs placebo | | | | | Rosenfalck, 2002 | Orlistat vs placebo | | | | | Rossner, 2000 | Orlistat vs placebo | | | | | Shi Yi, 2001 | Orlistat vs placebo | | | | | Sjostrom, 1998 | Orlistat vs placebo | | | | | Vidgren, 1999 | Orlistat vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Bakris, 2002 | orlistat (n=278) vs. placebo (n=276) | obese individuals with inadequately controlled hypertension.
| double-blind Sample size: 278/276 Primary endpoint: FU duration: 1-year | | Broom, 2002 | orlistat (n=265) vs. placebo (n=261) | obese patients with cardiovascular risk | double-blind parallel group Sample size: 265/261 Primary endpoint: FU duration: 54-week | | Broom,, 2001 | (n=71) vs. (n=71) | | Sample size: 71/71 Primary endpoint: FU duration: | | Davidson, 1999 | orlistat, 120 mg 3 times a day, for 52 weeks (n=668) vs. placebo (n=224) | Obese adults (BMI 30-43 kg/m2) | double-blind Sample size: 668/224 Primary endpoint: FU duration: 52 weeks | | Deerochanawong,, 2001 | (n=126) vs. (n=126) | | Sample size: 126/126 Primary endpoint: FU duration: | | Derosa, 2003 | orlistat 120 mg TID (n=27) vs. placebo (n=23) | obese patients with hypercholesterolemia | double-blind Sample size: 27/23 Primary endpoint: FU duration: 1-year | | Gotfredsen, 2001 | (n=16) vs. (n=14) sous groupe | | Sample size: 16/14 Primary endpoint: FU duration: | | Halpern, 2003 | orlistat (120 mg t.i.d.), (n=169) vs. placebo (n=174) | Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2 | Double-blind parallel Sample size: 169/174 Primary endpoint: FU duration: 24 weeks | | Hanefeld, 2002 | orlistat 120 mg t.i.d. (n=195) vs. placebo (n=188) | Overweight or obese adults (BMI >or= 28 kg/m2) with HbA1c of 6.5-11% and clinical type 2 diabetes | double-blind Sample size: 195/188 Primary endpoint: FU duration: 48-week | | Hauptman, 2000 | 60 mg of orlistat TID or 120 mg of orlistat TID, (n=210) vs. placebo (n=212) | obese patients (BMI 30-44 kg/m2) | double-blind Sample size: 210/212 Primary endpoint: FU duration: 1 year | | Hill, 1999 | 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for 1 y (n=181) vs. placebo (n=188) | Obese subjects who lost > or = 8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy | double-blind Sample size: 181/188 Primary endpoint: FU duration: 1 year | | Hollander, 1998 | 120 mg orlistat orally three times a day (n=163) vs. placebo (n=159) | obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas | double-blind Sample size: 163/159 Primary endpoint: FU duration: 57-week | | Karhunen, 2000 | orlistat 120 mg t.i.d.
(n=36) vs. placebo (n=36) | obese subjects | double-blind Sample size: 36/36 Primary endpoint: FU duration: 1 y. | | Kelley, 2002 | orlistat 120 mg three times a day (n=274) vs. placebo (n=276) | overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%) | double-blind Sample size: 274/276 Primary endpoint: FU duration: 1-year | | Krempf, 2005 | orlistat 120 mg three times daily (n=346) vs. placebo (n=350) | otherwise healthy, overweight patients aged 18-65 y (BMI >or=28 kg/m2 | double-blind Sample size: 346/350 Primary endpoint: FU duration: 18-month | | Lindgarde, 2000 | orlistat 120 mg three times daily (n=190) vs. placebo (n=186) | obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension | double-blind Sample size: 190/186 Primary endpoint: FU duration: 1 year | | Lucas, 2003 | (n=256) vs. (n=188) | | Sample size: 256/188 Primary endpoint: FU duration: | | Micic, 1999 | orlistat 120 mg three times daily (n=60) vs. placebo (n=59) | obese patients (BMI > or = 30 kg/m2) with hyperlipidemia (LDL-cholesterol > or = 4, 2 mmol/l) | double-blind Sample size: 60/59 Primary endpoint: FU duration: 24 weeks | | Miles, 2002 | 120 mg orlistat t.i.d. (n=255) vs. placebo (n=261) | overweight and obese patients with suboptimal control of type 2 diabetes | double-blind Sample size: 255/261 Primary endpoint: FU duration: 1 year | | Muls, 2001 | orlistat 120 mg three times daily (n=147) vs. placebo (n=147) | obese hypercholesterolemic patients, BMI between 27-40 kg/m2 and low-density-lipoprotein cholesterol, LDL-C, between 4.1-6.7 mmol/l | double-blind Sample size: 147/147 Primary endpoint: FU duration: 24 week | | Naumov, 2002 | orlistat (n=15) vs. diet alone (n=15) | patients with stable angina pectoris concomitant with obesity and hyperlipemia | open Sample size: 15/15 Primary endpoint: FU duration: | | Reaven, 2001 | (n=156) vs. (n=91) | | Sample size: 156/91 Primary endpoint: FU duration: | | Rissanen, 2001 | orlistat 120 mg three times daily (n=25) vs. placebo (n=26) | healthy obese women | double-blind Sample size: 25/26 Primary endpoint: FU duration: 12-month | | Rosenfalck, 2002 | (n=3) vs. (n=1) | obese patients | Sample size: 3/1 Primary endpoint: FU duration: | | Rossner, 2000 | orlistat (60 or 120 mg) three times a day (n=244) vs. Obese patients (body mass index 28 to 43 kg/m2) (n=243) | Obese patients (body mass index 28 to 43 kg/m2) | double-blind Sample size: 244/243 Primary endpoint: FU duration: 2-year | | Shi Yi, 2001 | (n=986) vs. (n=142) | | Sample size: 986/142 Primary endpoint: FU duration: | | Sjostrom, 1998 | orlistat 120 mg (three times a day) (n=345) vs. (n=343) | | double-blind Sample size: 345/343 Primary endpoint: FU duration: 1 year | | Vidgren, 1999 | 120 mg of orlistat three times a day (n=37) vs. placebo (n=38) | obese subjects | Sample size: 37/38 Primary endpoint: FU duration: 1 year |
|
| weight-loss drugs | phentermine and topiramate | versus placebo or control No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| OB 301 (mid-dose) | PHEN/TPM mid-dose vs placebo | | | | | OB 302 (low-dose) | PHEN/TPM low-dose vs placebo | | | | | CONQUER (mid-dose) (OB 303) | PHEN/TPM mid-dose vs placebo | | | | | CONQUER (high-dose) (OB 303) | PHEN/TPM high dose vs placebo | | | | | OB 302 (high-dose) | PHEN/TPM high dose vs placebo | | | | | OB 301 (high-dose) | PHEN/TPM high dose vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| OB 301 (mid-dose) | PHEN/TPM 7.5/46 mg (n=107) vs. placebo (n=109) 3 arms: PHEN/TPM 3.75/23 mg, PHEN/TPM
15/92 mg and placebo | | Parallel groups Sample size: 107/109 Primary endpoint: Weight loss at 28 weeks FU duration: 28 weeks | | OB 302 (low-dose) | PHEN/TPM 3.75/23 mg (n=241) vs. placebo (n=514) | | Sample size: 241/514 Primary endpoint: Weight loss at 56 weeks FU duration: 56 weeks | | CONQUER (mid-dose) (OB 303) | PHEN/TPM 7.5/46 mg (n=498) vs. placebo (n=994) | | Sample size: 498/994 Primary endpoint: Weight loss at 56 weeks FU duration: 56 weeks | | CONQUER (high-dose) (OB 303) | PHEN/TPM 15/92 mg (n=995) vs. placebo (n=994)
|
| Sample size: 995/994 Primary endpoint: Weight loss at 56 weeks FU duration: 56 weeks
| | OB 302 (high-dose) | PHEN/TPM 15/92 mg (n=512) vs. placebo (n=514)
|
| Sample size: 512/514 Primary endpoint: Weight loss at 56 weeks FU duration: 56 weeks
| | OB 301 (high-dose) | PHEN/TPM 15/92 mg (n=108) vs. placebo (n=109) 3 arms: PHEN/TPM 3.75/23 mg, PHEN/TPM
15/92 mg and placebo
|
| Sample size: 108/109 Primary endpoint: Weight loss at 28 weeks FU duration: 28 weeks
|
|
| weight-loss drugs | Sibutramine | versus placebo or control No demonstrated result for efficacy sibutramine inferior to placebo in terms of cardiovascular events in SCOUT, 2010 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| McMahon, 2000 | Sibutramine vs placebo | | | | | McMahon, 2002 | Sibutramine vs placebo | | | | | Smith, 2001 | Sibutramine vs placebo | | | | | SCOUT, 2010 | sibutramine vs placebo | | cardiovascular events 1.16 [1.03; 1.31] | |
| Trial | Treatments | Patients | Method |
|---|
| McMahon, 2000 | (n=142) vs. (n=157) | | Sample size: 142/157 Primary endpoint: FU duration: | | McMahon, 2002 | (n=145) vs. (n=72) | | Sample size: 145/72 Primary endpoint: FU duration: | | Smith, 2001 | (n=142) vs. (n=69) | | Sample size: 142/69 Primary endpoint: FU duration: | | SCOUT, 2010 | sibutramine (n=4906) vs. placebo (n=4898) | overweight or obese patients with diabetes or a history of coronary or peripheral vascular disease or stroke, along with other CV risk factors | double blind Parallel groups Sample size: 4906/4898 Primary endpoint: death, MI, stroke FU duration: 3.4 year |
|
| weight-loss drugs | topiramate | versus placebo or control No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Bray, 2003 | Topiramate vs placebo | | | | | Caterson, 2003 | Topiramate vs placebo | | | | | Pud’homme, 2003 | Topiramate vs placebo | | | | | Rissanen, 2003 | Topiramate vs placebo | | | | | Stenlof, 2003 | Topiramate vs placebo | | | | | Tonstad, 2003 | Topiramate vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Bray, 2003 | (n=75) vs. (n=75) | | Sample size: 75/75 Primary endpoint: FU duration: | | Caterson, 2003 | (n=93) vs. (n=97) | | Sample size: 93/97 Primary endpoint: FU duration: | | Pud’homme, 2003 | (n=33) vs. (n=33) | | Sample size: 33/33 Primary endpoint: FU duration: | | Rissanen, 2003 | (n=123) vs. (n=103) | | Sample size: 123/103 Primary endpoint: FU duration: | | Stenlof, 2003 | (n=135) vs. (n=137) | | Sample size: 135/137 Primary endpoint: FU duration: | | Tonstad, 2003 | (n=178) vs. (n=177) | | Sample size: 178/177 Primary endpoint: FU duration: |
|
