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CLINICAL GUIDELINES

Meta-Analysis: Pharmacologic Treatment of Obesity

Zhaoping Li, MD, PhD; Margaret Maglione, MPP; Wenli Tu, MS; Walter Mojica, MD; David Arterburn, MD, MPH; Lisa R. Shugarman, PhD; Lara Hilton, BA; Marika Suttorp, MS; Vanessa Solomon, MA; Paul G. Shekelle, MD, PhD; and Sally C. Morton, PhD

5 April 2005 | Volume 142 Issue 7 | Pages 532-546

Background: In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used.

Purpose: To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss.

Data Sources: Electronic databases, experts in the field, and unpublished information.

Study Selection: Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively.

Data Extraction: The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication.

Data Synthesis: All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, –1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported.

Limitations: Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses.

Conclusions: Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.

Editors' Notes Context The effectiveness of pharmacologic therapy in the treatment of obesity is unclear. Contribution This review of 79 clinical trials involving diet plus the obesity drugs sibutramine, orlistat, fluoxetine, sertraline, bupropion, topiramate, or zonisamide shows that these medications can lead to modest weight reductions of approximately 5 kg or less at 1 year. Available evidence is lacking on the effect of these drugs on long-term weight loss, health outcomes such as cardiovascular events and diabetes, and adverse effects. Implications Those considering pharmacologic treatment for obesity should understand that these drugs can lead to modest weight loss at 1 year, but data on long-term effectiveness and safety are lacking. –The Editors

 

Author and Article Information

From the Southern California Evidence-Based Practice Center, which includes RAND Health Division, Santa Monica, and the Greater Los Angeles VA Healthcare System, Los Angeles, California; and Department of Veterans Affairs, Cincinnati, Ohio.

Disclaimer: The authors of this article are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

Acknowledgments: The authors thank Alison Avenell for allowing us access to the National Health Service Health Technology Assessment report.

Grant Support: This article was supported by a contract to the Southern California Evidence-based Practice Center from the Agency for Healthcare Quality and Research.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Zhaoping Li, MD, PhD, West LA Veterans Affairs Medical Center, W111A, 11301 Wilshire Boulevard, Los Angeles, CA 90073.

Current Author Addresses: Drs. Li and Shekelle: West LA Veterans Affairs Medical Center, W111A, 11301 Wilshire Boulevard, Los Angeles, CA 90073.

Dr. Maglione, Mr. Tu, Dr. Mojica, Dr. Shugarman, Ms. Hilton, Ms. Suttorp, and Dr. Morton: RAND, 1776 Main Street, Santa Monica, CA 90407.

Dr. Arterburn: Cincinatti Veterans Affairs Medical Center, 3200 Vine Street, Cincinatti, OH 45220.

Ms. Solomon: Charles Drew University, 1748 East 118th Street, Building N, Los Angeles, CA 90059.

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