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Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis.
JAMA. 2016 Jun 14; 315(22):2424-34.JAMA

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 29 018 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.

Authors+Show Affiliations

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City.Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota3Division of Preventive Medicine, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, Ohio.Division of Gastroenterology, University of California, San Diego, La Jolla.Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.Department of Library Services, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology, University of California, San Diego, La Jolla.Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology, University of California, San Diego, La Jolla8Division of Biomedical Informatics, University of California, San Diego, La Jolla.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Review
Systematic Review

Language

eng

PubMed ID

27299618

Citation

Khera, Rohan, et al. "Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: a Systematic Review and Meta-analysis." JAMA, vol. 315, no. 22, 2016, pp. 2424-34.
Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016;315(22):2424-34.
Khera, R., Murad, M. H., Chandar, A. K., Dulai, P. S., Wang, Z., Prokop, L. J., Loomba, R., Camilleri, M., & Singh, S. (2016). Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA, 315(22), 2424-34. https://doi.org/10.1001/jama.2016.7602
Khera R, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: a Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34. PubMed PMID: 27299618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. AU - Khera,Rohan, AU - Murad,Mohammad Hassan, 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 - 2016/6/15/entrez PY - 2016/6/15/pubmed PY - 2016/6/23/medline SP - 2424 EP - 34 JF - JAMA JO - JAMA VL - 315 IS - 22 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 29 018 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/27299618/Association_of_Pharmacological_Treatments_for_Obesity_With_Weight_Loss_and_Adverse_Events:_A_Systematic_Review_and_Meta_analysis_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.7602 DB - PRIME DP - Unbound Medicine ER -