Long-term pharmacotherapy for obesity and overweight

Abstract

Background: Obesity is a highly and increasingly prevalent chronic condition for which drugs are commonly prescribed to improve health. Objectives: To assess the long-term effects of approved anti-obesity medications in clinical trials of at least one-year duration. Search methods: MEDLINE, EMBASE, The Cochrane Library, the Current Science Meta-register of Controlled Trials and reference lists were searched. Drug manufacturers and two obesity experts were contacted. Selection criteria: Double-blind, randomised placebo-controlled trials of approved anti-obesity agents that 1) included patients over 18 years, 2) used an intention-to-treat analysis, and 3) had follow-up of one year or more. Both weight loss and weight maintenance trials were included. Abstracts, pseudo-randomised trials, head-to-head trials and open-label studies were excluded. Data collection and analysis: Two reviewers independently assessed all potentially relevant reports for inclusion and methodological quality. Data were extracted using double data entry. The primary outcome measure was weight loss. Main results: Sixteen orlistat (n = 10,631), 10 sibutramine (n = 2623) and four rimonabant trials (n = 6365) met inclusion criteria. Attrition rates averaged 30% to 40%. Compared to placebo, orlistat reduced weight by 2.9 kg (95% confidence interval (CI) 2.5 to 3.2 kg), sibutramine by 4.2 kg (95% CI 3.6 to 4.7 kg), and rimonabant by 4.7 kg (95% CI 4.1 to 5.3 kg). Patients on active drug therapy were significantly more likely to achieve 5% and 10% weight loss thresholds. Placebo-controlled weight losses were consistently lower in patients with diabetes. Orlistat reduced diabetes incidence, improved total cholesterol, LDL-cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered HDL levels. Sibutramine improved HDL and triglyceride levels but raised blood pressure and pulse rate. Rimonabant improved HDL-cholesterol, triglyceride and blood pressure levels and glycaemic control in patients with diabetes but increased the risk of mood disorders. Authors' conclusions: Orlistat, sibutramine and rimonabant have been studied in trials of one year or longer. Internal validity of studies was limited by high attrition rates. All three antiobesity agents are modestly effective in reducing weight and have differing effects on cardiovascular risk and adverse effects profiles. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required.