Key messages

• The effects of three weight‐reducing medicines (orlistat, phentermine/topiramate and naltrexone/bupropion) on death rates and cases of heart disease are unclear for people with hypertension (high blood pressure) due to a lack of reliable evidence. There is no information about these measures for the medicines semaglutide and tirzepatide.
• Taking phentermine/topiramate or naltrexone/bupropion probably causes more unwanted events in people with hypertension than taking a placebo (inactive 'dummy' medicine). Taking orlistat probably causes an increase in the number of serious unwanted effects compared to taking a placebo. We did not find any information about side effects for people with hypertension taking semaglutide or tirzepatide.
• Long‐term studies are needed to assess the effects of medicines used for weight management on death rates and heart and blood vessel problems in people with hypertension. It is also important that results for people with hypertension be provided by authors of any completed study that included people with and without hypertension.

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 numbers: 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. The risk of developing high blood pressure (hypertension) increases with age.

Why is hypertension a problem?

Hypertension can increase the risk of developing serious 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 diseases), which leads to fewer deaths and cardiovascular problems.

Is there a link between being overweight and hypertension?

Being overweight is associated with increased blood pressure. Hypertension treatment guidelines recommend maintaining a healthy weight and losing weight when needed. Some people may take medicine specifically to help reduce their weight.

What do we want to find out?

We wanted to find out if weight‐loss medicines could reduce the negative effects of hypertension on people's health.

What did we do?

We updated a systematic review. We looked for studies on how weight‐loss medicines affect people with hypertension. We wanted to know how many people experienced unwanted events (e.g. side effects), how many developed heart disease or stroke, and if any died.

We looked for studies called 'randomised controlled trials', which usually give the most reliable evidence about the effects of a treatment. We rated how certain we were about the evidence, taking into account how the studies were done, how many people took part and whether results were consistent. All studies compared a weight‐loss medicine with a placebo, which is a 'dummy' medicine, one that looks like the same medicine but is inactive.

What did we find?

We added two new studies of medicines recently approved for weight reduction, so, in total, this updated review includes eight studies. They involved around 13,000 people with hypertension (average age 46 to 62 years). Three studies were conducted in the USA, three in European countries and two were multinational. The studies lasted between six and 48 months. Pharmaceutical companies funded seven of the eight studies.

For people with hypertension, three drugs that are approved to help people lose weight over time (orlistat, phentermine/topiramate and naltrexone/bupropion) may make little to no difference to how many people die or how many people have heart problems, but we are very uncertain about the results. People taking orlistat, phentermine/topiramate and naltrexone/bupropion probably have more serious unwanted events than those taking placebo. However, there may be little to no difference in unwanted events in general between orlistat and placebo, and little to no difference in serious unwanted events between phentermine/topiramate and placebo, but we are very uncertain about these results. The most common unwanted events were digestive problems (for orlistat, phentermine/topiramate), and dry mouth and skin tingling or numbness (for naltrexone/bupropion).

The studies that investigated semaglutide or tirzepatide did not present information on the number of deaths, heart problems or safety issues in people with hypertension.

What are the limitations of the evidence?

We are not confident in the evidence regarding overall deaths and heart problems for orlistat, phentermine/topiramate or naltrexone/bupropion, or regarding serious unwanted events for phentermine/topiramate, because of our concerns about how the studies were conducted and the low number of the events. We are not confident in the evidence about all unwanted events for orlistat because of our concerns about how the studies were conducted and because the results were inconsistent across different studies. We have more confidence in the evidence regarding serious unwanted events for orlistat and naltrexone/bupropion, and regarding all unwanted events for phentermine/topiramate or naltrexone/bupropion, but we do not have high certainty about these because of our concerns about how some of the studies were conducted.

How up to date is the evidence?

The evidence is up to date to April 2024.