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
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.
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Electronic databases, experts in the field, and unpublished information.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, âˆ’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.
HTA = Health Technology Assessment; NHS = National Health Service. *See the companion article by Maggard et al. in this issue. †These 39 articles were randomized, controlled trials and reviews of sibutramine, phentermine, and diethylpropion.
Data are from reference 35. = 0.14 (chi-square test); I2 = 43%.
= 0.00 (chi-square test); I2 = 83%.
For bupropion, = 0.00 (chi-square test) and I2 = 84%. For fluoxetine, = 0.00 (chi-square test) and I 2= 85%.
= 0.00 (chi-square test) and I2 = 87%.
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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.
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