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; Sally C. Morton, PhD
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.
In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used.
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.
Electronic databases, experts in the field, and unpublished information.
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.
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.
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.
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.
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.
The effectiveness of pharmacologic therapy in the treatment of obesity is unclear.
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.
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.
Table 1. Prescription Medications Used for Weight Loss
Pooled analysis of weighted mean difference in weight loss with sibutramine versus placebo at 44 to 54 weeks.P
Pooled analysis of mean difference in weight loss with orlistat versus placebo at 12 months.P
Pooled analysis of weight loss with bupropion and fluoxetine versus placebo at 6 to 12 months.PP
Pooled analysis of weight loss with topiramate versus placebo at 6 months.P
Table 2. Summary of Findings on Medications for Weight Loss
Table 3. Summary of Findings regarding Adverse Events according to Medications for Weight Loss
Table 4. Summary of Side Effects of Sibutramine Used for Weight Loss
Appendix Table. Evidence Table of Randomized, Controlled Trials
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Kishore M Gadde
May 2, 2005
Meta-analysis of pharmacologic treatment of obesity utilised irrelevant data
For assessing weight loss efficacy of bupropion in the treatment of obesity, Li et al have pooled data from 3 RCTs.
It is rather amusing that the largest data for bupropion's weight loss efficacy in this meta-analysis came from a trial (Croft et al 2002) assessing antidepressant efficacy of bupropion in patients with major depression. The primary outcome in that trial was not weight loss. The primary diagnosis of these patients was not obesity. Most of the patients in the study were not even obese. These patients did not enter this trial with the intent of losing weight. Bupropion was not tested in this trial for its weight loss.
Li et al have erred in including data from this DEPRESSION study in a meta-analysis of pharmacologic treatment of OBESITY. These investigators have failed to see the difference between INTENTIONAL weight loss as the desired effect and a SIDE EFFECT reported in a sample that is not the topic of this meta-analysis.
Received research funding from GSK, Lilly, Elan and Forest Labs.
Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, et al. Meta-Analysis: Pharmacologic Treatment of Obesity. Ann Intern Med. 2005;142:532–546. doi: 10.7326/0003-4819-142-7-200504050-00012
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Published: Ann Intern Med. 2005;142(7):532-546.
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