Key messages

• Compared to placebo (a sham medication), tirzepatide likely helps adults with obesity lose weight in the medium term (up to 2 years), and this weight reduction is likely to be maintained over the long term (more than 2 years). Tirzepatide may increase the risk of non-serious unwanted effects in the medium and long term, but may have little to no effect on serious unwanted effects, including those that cause people to stop taking tirzepatide. It may have little to no effect on quality of life, major cardiovascular events, and mortality.

• The manufacturer of tirzepatide was involved in the funding, design, running and reporting of all nine included studies. This raises concerns about conflicts of interest that might affect the results. More independent research is needed.

What is obesity?

Obesity is a condition in which a person has too much body fat, which can increase the risk of health problems like type 2 diabetes, heart disease, and some types of cancer. Managing obesity often involves lifestyle changes such as eating a healthier diet and being more physically active. In some cases, doctors may prescribe medications to support weight loss.

What is tirzepatide?

Tirzepatide is a medication developed to treat people living with obesity or weight-related health problems. It works by mimicking two hormones that help to regulate appetite, stomach emptying, feeling full, blood sugar, and metabolism. It is given as a weekly injection. Some people taking tirzepatide experience unwanted effects, such as indigestion, feeling sick, diarrhoea, and constipation. Other similar medications are liraglutide and semaglutide.

What did we want to find out?

We wanted to know how well tirzepatide works in adults with obesity in the medium term (up to 2 years) and long term (2 or more years). We examined its effects on weight loss, health problems associated with obesity, unwanted effects, quality of life, and risk of death. We did not look at what happens after people stop taking tirzepatide.

What did we do?

We searched for studies that compared tirzepatide with placebo (a sham treatment), no treatment, lifestyle changes or another weight-loss medication. We focused on studies that compared tirzepatide with placebo. We included studies that followed participants for at least six months. We analysed the results and rated our confidence in the evidence.

What did we find?

We included nine studies involving 7111 adults with obesity, aged 36 to 65 years, mainly from middle- and high-income countries. Eight studies compared tirzepatide with placebo, and 1 study compared tirzepatide with semaglutide. Tirzepatide was given as a weekly injection in doses ranging from 5 mg to 15 mg. The main comparison with placebo (8 studies, 6361 people) has the following findings.

• Tirzepatide likely results in significant weight loss in the medium term (up to about 1.5 years) and probably maintains this effect in the long term (around 3.5 years).

• People taking tirzepatide may experience non-serious unwanted effects, but may be no more or less likely to discontinue treatment because of these effects than people taking a placebo. There may be little or no difference in serious unwanted effects.

• Tirzepatide may result in little to no difference in cardiovascular events, but it might not improve quality of life or decrease mortality.

What are the limitations of the evidence?

Our confidence in the evidence is limited because of concerns about how some of the studies were conducted. The long-term findings are based on only one study. The manufacturer of tirzepatide funded all the studies, which raises concerns about the reliability of the results. More independent research is needed.

How up to date is this evidence?

The evidence is up to date as of December 2024.