What is high blood pressure (hypertension)?
Blood pressure is a measure of the force that your heart uses to pump blood around your body. It is usually given as two figures: the pressure when your heart pushes blood out (systolic pressure), and the pressure when your heart rests between beats (diastolic pressure). Blood pressure is considered to be high when systolic pressure is over 140 and/or diastolic pressure is over 90, often written as '140 over 90' and measured in millimetres of mercury (mm Hg). The risk of developing high blood pressure increases as you get older.
Hypertension can increase people's risk of developing serious long-term health problems, such as heart attack or stroke. Lowering blood pressure in people with hypertension reduces the number of people who develop diseases of the heart and blood vessels (cardiovascular disease), which leads to fewer deaths and cardiovascular problems.
Weight and hypertension
Hypertension treatment guidelines recommend keeping to a healthy weight and losing weight when needed. Some people may take medicines to help reduce their weight.
Why we did this Cochrane Review
Medicines licensed for use in weight loss in the USA and Europe include orlistat and naltrexone combined with bupropion. Another combination, phentermine with topiramate, is licensed in the USA only. We wanted to find out if weight-loss medicines have long-lasting effects on blood pressure, and whether they could reduce the unwanted effects of high blood pressure on people's health.
What did we do?
We searched for studies about the effects of taking weight-loss medicines in people with high blood pressure. We were interested in how these medicines affected blood pressure and body weight. We also wanted to know how many people experienced any unwanted effects, how many people developed cardiovascular disease, and if any people died.
We looked for randomised controlled studies, in which the treatments people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a treatment.
We assessed the reliability of the evidence we found. We considered factors such as: how the studies were conducted, how many people they involved, and whether their findings were consistent across studies.
Search date: we included evidence published up to March 2020.
What we found
We found six studies in 12,724 people with high blood pressure (average age 46 to 62 years). The studies were conducted in the USA (3 studies) and Europe (3 studies), and lasted from 6 months to 28 months.
All studies compared the effects of taking a weight-loss medicine with effects of taking a dummy medicine (placebo).
What are the results of our review?
Orlistat may reduce weight and probably reduces blood pressure (4 studies; 2058 people).
Phentermine plus topiramate may reduce weight and may reduce blood pressure (1 study; 1305 people).
Naltrexone plus bupropion probably reduces weight but probably does not reduce blood pressure (1 study; 8283 people).
One study looked at the risk of death and major unwanted cardiovascular effects; it showed no differences between naltrexone plus bupropion treatment and a placebo after two years.
People taking weight-loss medicines reported more unwanted effects than those taking a placebo. The most common unwanted effects were digestive problems (for orlistat, and phentermine plus topiramate), dry mouth and skin tingling or numbness (for naltrexone plus bupropion).
How reliable are these results?
Results are from a small number of studies. In some studies, there were few events for some measures we were interested in.
We are moderately confident about how orlistat and naltrexone plus bupropion affected weight loss and blood pressure. However, results might change if more evidence becomes available.
We are less confident about the effects of phentermine plus topiramate; the unwanted effects of orlistat, and the risk of unwanted cardiovascular events associated with naltrexone plus bupropion. Results are likely to change if more evidence becomes available.
Conclusions
Some weight-loss medicines reduce weight and blood pressure in people with high blood pressure, but may cause unwanted effects. We did not find enough evidence about whether taking weight-loss medicines to lose weight could reduce death and cardiovascular disease.
In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.
This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.
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 and diastolic blood pressure, and on body weight reduction.
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.
Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.
Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.
This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes.
There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) −2.6 mm Hg (95% confidence interval (CI) −3.8 to −1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD −2.0 mm Hg (95% CI −2.7 to −1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by −2.0 to −4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by −1.3 to −1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.