Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials

Abstract

AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d > 0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.

Cardiovascular Risk-Benefit Profile of Sibutramine

“…[57] Indeed, because of its mode of action, sibutramine treatment could somewhat dampen the classically observed reduction in arterial BP resulting from weight loss as shown in several meta-analyses. [50,53,[58][59][60] In a meta-analysis of 21 double-blind, randomised controlled trials of sibutramine, modest increases in systolic and diastolic BP were observed in patients treated with sibitramine as compared to placebo. [58] These results were confirmed in another meta-analysis of seven long-term studies.…”

Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials

“…Previous reviews that have included studies up to December 2000 suggest that the magnitude of weight loss induced by such agents is approximately 5 kg or less. [21][22][23] However, shortterm efficacy is a suboptimal end point, especially if recidivism is common when therapy is stopped. The longterm safety of antiobesity medications is also a concern given previous evidence linking fenfluramine and dexfenfluramine to valvular heart disease and pulmonary hypertension, and recent concerns regarding sibutramine and increased cardiovascular risk.…”

Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification

“…These weight losses are similar to those reported for orlistat in a recent pharmacotherapy meta-analysis, where orlistat yielded an average weight loss of 7.1 kg in six randomized, placebo-controlled trials. 34 In addition, substantial proportions of OLM-treated patients achieved the thresholds regarded by the US Food and Drug Administration as desirable. 35 Nearly 60% of completers (41% ITT) lost 5% of initial body weight at 12 months and 31% of completers (21.4% ITT) lost 10% of initial body weight (see Figure 3).…”

“…36,38 While we could not examine ethnic differences in weight loss, treated Mexican- American participants achieved weight losses similar to those reported in previous orlistat trials. 34 This study focused on demonstrating weight loss in an underserved population; thus we limited our enrollment to overweight and obese Mexican-American women primarily with class I and II obesity 1 without substantial medical comorbidities, similar to most obesity drug studies. 24 It was not surprising that we did not significantly impact some of the secondary outcomes such as blood pressure.…”

“…While some previous studies have reported that ethnic minorities are less likely to achieve benefits from participating in obesity management trials, 16,17 the results of this study with Mexican-American women suggest that the combination of orlistat with a culturally appropriate lifestyle intervention can produce weight losses similar to those reported in other orlistat trials. 34 …”