Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events

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 MEASURESProportions 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,; 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,) 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.

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“…They reported that orlistat presented a mean reduction of 2.6 kilograms among overweight and obese adults [16]. In our study we observed that 74% of the subjects lost weight (41/55), and that weight reduction had a mean value of 2.17 kilograms.…”

“…We found statistic differences between those who lose waist centimeters and those who gained waist centimeters (Chi-square, p = 0.000). to placebo [16]. In our study, 17% (4/41) of those who lose weight lost 5% of their initial body weight during the same period of time (52 weeks).…”

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“…The resulting fat malabsorption facilitates a negative energy state leading to a placebo-subtracted weight loss in the range of 2.6% (Davidson et al, 1999;Khera et al, 2016). Orlistat has additional beneficial effects on glycemic control and nonalcoholic fatty liver disease (Hollander et al, 1998;Zelber-Sagi et al, 2006).…”

“…Lorcaserin has been reported to promote satiety to elicit a 3.2% placebo-subtracted body weight loss in overweight and obese adults (Smith et al, 2010;Khera et al, 2016). Mechanism of action presumably involves activation of hypothalamic POMC neurons (Xu et al, 2008;Berglund et al, 2013), without impacting energy expenditure (Martin et al, 2011).…”

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“…Phentermine is indicated as short-term (a few weeks) adjunct in conjunction with lifestyle and behavioral weight loss interventions (29). Five weight loss medications (or combination medications) are FDA-approved for longterm use (more than a few weeks) by patients with BMI $27 kg/m 2 with one or more obesity-associated comorbid conditions (e.g., type 2 diabetes, hypertension, and dyslipidemia) and by patients with BMI $30 kg/m 2 who are motivated to lose weight (30)(31)(32)(33)(34). Medications approved by the FDA for the treatment of obesity and their advantages and disadvantages are summarized in Table 7.2.…”