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.


OBJECTIVE



OBJECTIVE
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


OBJECTIVE
- changes in systolic and/or diastolic blood pressure - body weight reduction


METHODS
Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews.


METHODS
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.


METHODS
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.


RESULTS
Eight studies comparing orlistat or sibutramine to placebo fulfilled 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.


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 needed.
Siebenhofer
Andrea
A
Department of Internal Medicine and Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria, 8036.
Horvath
Karl
K
Jeitler
Klaus
K
Berghold
Andrea
A
Stich
Anne K
AK
Matyas
Eva
E
Pignitter
Nicole
N
Siering
Ulrich
U
D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D003503:Cyclobutanes / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000077403:Orlistat; D010880:Piperidines / Q000009:adverse effects; D011720:Pyrazoles / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000077285:Rimonabant; D013995:Time; D015431:Weight Loss
D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D007783:Lactones; D010880:Piperidines; D011720:Pyrazoles; D000077403:Orlistat; D000077285:Rimonabant; C058254:sibutramine