Association of pharmacological treatments for obesity withweight loss and adverse events a systematic review and meta-analysis

Rohan Khera, Mohammad H Murad, Apoorva K. Chandar, Parambir S. Dulai, Zhen Wang, Larry J. Prokop, Rohit Loomba, Michael Camilleri, Siddharth Singh

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Importance Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE,Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5%weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29018 patients (median age, 46 years; 74%women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23%of placebo participants had at least 5%weight loss vs 75%of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95%credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63%of participants taking liraglutide (OR, 5.54; 95%CrI, 4.16-7.78; SUCRA, 0.83), 55%taking naltrexone-bupropion (OR, 3.96; 95%CrI, 3.03-5.11; SUCRA, 0.60), 49%taking lorcaserin (OR, 3.10; 95%CrI, 2.38-4.05; SUCRA, 0.39), and 44%taking orlistat (OR, 2.70; 95%CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95%CrI,-10.20 to-7.42 kg); liraglutide, 5.3 kg (95%CrI,-6.06 to-4.52 kg); naltrexone-bupropion, 5.0 kg (95%CrI,-5.94 to-3.96 kg); lorcaserin, 3.2 kg (95%CrI,-3.97 to-2.46 kg); and orlistat, 2.6 kg (95%CrI,-3.04 to-2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95%CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95%CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45%in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5%weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5%weight loss.

Original languageEnglish (US)
Pages (from-to)2424-2434
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume315
Issue number22
DOIs
StatePublished - Jun 14 2016

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Phentermine
Bupropion
Naltrexone
Meta-Analysis
Weight Loss
Obesity
Odds Ratio
Pharmacology
Placebos
Therapeutics
Randomized Controlled Trials
Anti-Obesity Agents
Information Storage and Retrieval
United States Food and Drug Administration
Drug-Related Side Effects and Adverse Reactions
MEDLINE
Registries
Liraglutide
Body Mass Index
Body Weight

ASJC Scopus subject areas

  • Medicine(all)

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Association of pharmacological treatments for obesity withweight loss and adverse events a systematic review and meta-analysis. / Khera, Rohan; Murad, Mohammad H; Chandar, Apoorva K.; Dulai, Parambir S.; Wang, Zhen; Prokop, Larry J.; Loomba, Rohit; Camilleri, Michael; Singh, Siddharth.

In: JAMA - Journal of the American Medical Association, Vol. 315, No. 22, 14.06.2016, p. 2424-2434.

Research output: Contribution to journalArticle

Khera, Rohan ; Murad, Mohammad H ; Chandar, Apoorva K. ; Dulai, Parambir S. ; Wang, Zhen ; Prokop, Larry J. ; Loomba, Rohit ; Camilleri, Michael ; Singh, Siddharth. / Association of pharmacological treatments for obesity withweight loss and adverse events a systematic review and meta-analysis. In: JAMA - Journal of the American Medical Association. 2016 ; Vol. 315, No. 22. pp. 2424-2434.
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abstract = "Importance Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE,Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5{\%}weight loss and at least 10{\%} weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29018 patients (median age, 46 years; 74{\%}women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23{\%}of placebo participants had at least 5{\%}weight loss vs 75{\%}of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95{\%}credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63{\%}of participants taking liraglutide (OR, 5.54; 95{\%}CrI, 4.16-7.78; SUCRA, 0.83), 55{\%}taking naltrexone-bupropion (OR, 3.96; 95{\%}CrI, 3.03-5.11; SUCRA, 0.60), 49{\%}taking lorcaserin (OR, 3.10; 95{\%}CrI, 2.38-4.05; SUCRA, 0.39), and 44{\%}taking orlistat (OR, 2.70; 95{\%}CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95{\%}CrI,-10.20 to-7.42 kg); liraglutide, 5.3 kg (95{\%}CrI,-6.06 to-4.52 kg); naltrexone-bupropion, 5.0 kg (95{\%}CrI,-5.94 to-3.96 kg); lorcaserin, 3.2 kg (95{\%}CrI,-3.97 to-2.46 kg); and orlistat, 2.6 kg (95{\%}CrI,-3.04 to-2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95{\%}CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95{\%}CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30{\%}-45{\%}in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5{\%}weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5{\%}weight loss.",
author = "Rohan Khera and Murad, {Mohammad H} and Chandar, {Apoorva K.} and Dulai, {Parambir S.} and Zhen Wang and Prokop, {Larry J.} and Rohit Loomba and Michael Camilleri and Siddharth Singh",
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T1 - Association of pharmacological treatments for obesity withweight loss and adverse events a systematic review and meta-analysis

AU - Khera, Rohan

AU - Murad, Mohammad H

AU - Chandar, Apoorva K.

AU - Dulai, Parambir S.

AU - Wang, Zhen

AU - Prokop, Larry J.

AU - Loomba, Rohit

AU - Camilleri, Michael

AU - Singh, Siddharth

PY - 2016/6/14

Y1 - 2016/6/14

N2 - Importance Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE,Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5%weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29018 patients (median age, 46 years; 74%women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23%of placebo participants had at least 5%weight loss vs 75%of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95%credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63%of participants taking liraglutide (OR, 5.54; 95%CrI, 4.16-7.78; SUCRA, 0.83), 55%taking naltrexone-bupropion (OR, 3.96; 95%CrI, 3.03-5.11; SUCRA, 0.60), 49%taking lorcaserin (OR, 3.10; 95%CrI, 2.38-4.05; SUCRA, 0.39), and 44%taking orlistat (OR, 2.70; 95%CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95%CrI,-10.20 to-7.42 kg); liraglutide, 5.3 kg (95%CrI,-6.06 to-4.52 kg); naltrexone-bupropion, 5.0 kg (95%CrI,-5.94 to-3.96 kg); lorcaserin, 3.2 kg (95%CrI,-3.97 to-2.46 kg); and orlistat, 2.6 kg (95%CrI,-3.04 to-2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95%CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95%CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45%in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5%weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5%weight loss.

AB - Importance Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE,Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5%weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29018 patients (median age, 46 years; 74%women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23%of placebo participants had at least 5%weight loss vs 75%of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95%credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63%of participants taking liraglutide (OR, 5.54; 95%CrI, 4.16-7.78; SUCRA, 0.83), 55%taking naltrexone-bupropion (OR, 3.96; 95%CrI, 3.03-5.11; SUCRA, 0.60), 49%taking lorcaserin (OR, 3.10; 95%CrI, 2.38-4.05; SUCRA, 0.39), and 44%taking orlistat (OR, 2.70; 95%CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95%CrI,-10.20 to-7.42 kg); liraglutide, 5.3 kg (95%CrI,-6.06 to-4.52 kg); naltrexone-bupropion, 5.0 kg (95%CrI,-5.94 to-3.96 kg); lorcaserin, 3.2 kg (95%CrI,-3.97 to-2.46 kg); and orlistat, 2.6 kg (95%CrI,-3.04 to-2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95%CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95%CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45%in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5%weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5%weight loss.

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