title: 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.
  
  
  OBJECTIVE
  
  
  
  OBJECTIVE
  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).
  
  
  OBJECTIVE
  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.
  
  
  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).
  
  
  METHODS
  Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Institute of General Practice and Evidence-Based Health Services Research, Medical University of Graz, Graz, Austria / Institute of General Practice, Goethe University, Frankfurt am Main, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Siebenhofer
authors.forename: Klaus
authors.initials: K
authors.lastname: Jeitler
authors.forename: Karl
authors.initials: K
authors.lastname: Horvath
authors.forename: Andrea
authors.initials: A
authors.lastname: Berghold
authors.forename: Nicole
authors.initials: N
authors.lastname: Posch
authors.forename: Jutta
authors.initials: J
authors.lastname: Meschik
authors.forename: Thomas
authors.initials: T
authors.lastname: Semlitsch
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001067:Appetite Depressants / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003503:Cyclobutanes / Q000009:adverse effects / Q000627:therapeutic use; D004038:Diet, Reducing; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077403:Orlistat; D010645:Phentermine / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077285:Rimonabant; D056737:Safety-Based Drug Withdrawals; D013995:Time; D000077236:Topiramate; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D003503:Cyclobutanes; D007783:Lactones; D010880:Piperidines; D011720:Pyrazoles; D000077236:Topiramate; D005632:Fructose; D000077403:Orlistat; D010645:Phentermine; D000077285:Rimonabant; C058254:sibutramine