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

Siebenhofer A, Horvath K, Jeitler K, Berghold A, Stich AK, Matyas E, Pignitter N, Siering U

Published Online:

July 8, 2009

For overweight patients with elevated blood pressure doctors often recommend weight reduction. Drugs such as orlistat, sibutramine or rimonabant are sometimes suggested to assist in weight reduction and blood pressure reduction. Orlistat and sibutramine have been shown to modestly reduce weight. Orlistat also reduced blood pressure but sibutramine increased blood pressure. No study investigating rimonabant was found. No evidence is available for effects of any of these drugs on death or morbidity. The most frequent side effects were gastrointestinal for orlistat and dry mouth, constipation and headache for sibutramine.

Abstract (click to read)

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

Search strategy:

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

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:

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.

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 needed.

This record should be cited as:

Siebenhofer A, Horvath K, Jeitler K, Berghold A, Stich AK, Matyas E, Pignitter N, Siering U. Long-term effects of weight-reducing drugs in hypertensive patients. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007654. DOI: 10.1002/14651858.CD007654.pub2

Assessed as up to date:

May 6, 2009

Find the research

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Primary Review Group:

Hypertension Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are weight-reducing drugs in hypertensive patients?

Bottom line:

Although trials of orlistat and sibutramine in patients with elevated blood pressure demonstrated statistically significant decreases in weight, orlistat reduced blood pressure and sibutramine increased blood pressure.

Caveat:

No long term mortality and morbidity RCT evidence is available for these drugs. Trials of rimonabant in this patient population could not be included.

Context:

Orlistat, sibutramine and rimonabant are the main anti-obesity drugs in current use. Orlistat and sibutramine have been approved for long term treatment of obesity throughout much of the world. Rimonabant was approved for use in the European Union in 2006, and has also been approved in some South American and Asian countries. Rimonabant does not have US Food and Drug Administration (FDA) approval since preclinical and clinical data raised concerns about associations between rimonabant and increased frequency of psychiatric adverse events, including suicidality, an ill-defined constellation of neurological signs and symptoms, and seizures.¹ In January 2009, the European Commission issued a decision to withdraw market authorisation for rimonabant in all countries of the European Union.² 1.Food, Drug Administration. Egan AG. Colman EG. www.fda.gov/ohrms/dockets/AC/07/briefing/2007‐4306b1fda‐backgrounder.pdf 2.European Medicines Agency. www.emea.europa.eu/humandocs/PDFs/EPAR/acomplia/3945709en.pdf

Cochrane Systematic Review:

Siebenhofer A et al. Long term effects of weight-reducing drugs in hypertensive patients. Cochrane Reviews 2009, Issue 3. Article No. CD007654. DOI: 10.1002/14651858.CD007654.pub2. This review contains 8 studies involving 2726 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Heart & circulation > Hypertension > Treatment: pharmacological

Kidney disease > Hypertension > Treatment: pharmacological

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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