Long-term effects of weight-reducing drugs in hypertensive patients

Background All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option. Objectives Primary objectives: To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on: - all cause mortality - cardiovascular morbidity - adverse events Secondary objectives: - changes in systolic and/or diastolic blood pressure - body weight reduction even though sibutramine and rimonabant have been withdrawn from the market. Search methods Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews (status as of 17th August, 2012). Selection criteria Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo. Data collection and analysis Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity. Main results After the updated literature search, the number of studies remained the same, with eight studies comparing orlistat or sibutramine to placebo fulfilling our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95% CI +1.4 to +4.9 mm Hg. Authors' conclusions In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being.