Long‐term effects of weight‐reducing drugs in people with hypertension
Abstract
Background
All major guidelines on antihypertensive therapy recommend weight loss; anti‐obesity drugs may be able to help in this respect.
Objectives
Primary objectives:
To assess the long‐term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on all‐cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non‐serious adverse events).
Secondary objectives:
To assess the long‐term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction.
Search methods
We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015).
Selection criteria
Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long‐term pharmacologic interventions for weight loss with placebo.
Data collection and analysis
Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed‐effect meta‐analysis. When heterogeneity was present, we used the random‐effects method and investigated the cause of heterogeneity.
Main results
After updating the literature search, which was extended to include four new weight‐reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual‐care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by ‐2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): ‐4.0 to ‐0.9 mm Hg) and diastolic blood pressure by ‐1.9 mm Hg (MD; 95% CI: ‐3.0 to ‐0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure.
Authors' conclusions
In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long‐term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long‐term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.
PICOs
Plain language summary
Long‐term effects of weight‐reducing drugs in people with elevated blood pressure
Doctors often recommend that people who are overweight or obese with elevated blood pressure lose weight, which may include taking anti‐obesity drugs to assist in weight and blood pressure reduction. Two active ingredients (rimonabant and sibutramine) were withdrawn from the market in 2009 and 2010, respectively. Current guidelines for the pharmacological management of obesity quote five medications (orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide) that have been approved for long‐term weight reduction by the US Food and Drug Administration. However, two of these drugs (phentermine/topiramate and lorcaserin) did not obtain approval in Europe.
We found evidence that orlistat, sibutramine, and phentermine/topiramate modestly reduce weight. Orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We found no study investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. No evidence was available for the effects of any of these drugs on death or morbidity. The most common side effects were gastrointestinal for orlistat; dry mouth, constipation, and headache for sibutramine; and dry mouth and paresthaesia for phentermine/topiramate.
