BMJ: semaglutide reduced mortality in people with cardiovascular disease, but the meta-analysis does not confirm an overall class effect for obesity drugs
Major review finds that weight loss, cardiovascular protection, and longer survival do not align across obesity drugs
On 8 July, BMJ published a review of 262 randomized trials, in which participants were assigned at random to receive a drug or a comparator, involving nearly 100 thousand participants. The drugs differed substantially in their effects on weight, cardiovascular outcomes, adverse events, and quality of life. Subcutaneous semaglutide was the only treatment associated with a convincing reduction in all-cause mortality. This evidence came mainly from studies of people who already had a high risk of cardiovascular disease.
These drugs are commonly compared by the number of kilograms people lose. For someone who wants to live longer, that measure is too crude. Weight may fall quickly, while evidence on survival, cardiovascular function, and well-being remains specific to each drug.
The review compared 19 drugs and found that tirzepatide and the combination of cagrilintide with semaglutide produced the largest reductions in weight. Subcutaneous semaglutide reduced body weight by approximately 9,8% more than lifestyle changes alone. However, it was the only drug associated with a convincing reduction in all-cause mortality: 19% across 17 trials involving 25 264 participants. The risk of myocardial infarction was 28% lower.
The mortality reduction reported in this review applies to subcutaneous semaglutide in people with existing cardiovascular disease. Separate evidence is needed for people without diagnosed cardiovascular disease and for drugs with similar mechanisms because their absolute risks and outcomes may differ. Tirzepatide, for example, reduced the risk of heart failure, but the evidence for its effect on all-cause mortality is less certain.
Weight loss and quality-of-life scores did not align. The authors defined a difference of 10 points on the well-being scale as clinically meaningful. All drugs remained below this threshold, and subcutaneous semaglutide produced a score of 2,9 points. In a body-composition study of tirzepatide, participants lost fat but also lost lean mass, which includes muscle, water, and other components of the body.
For each drug, it is necessary to ask which specific outcome it changes: weight, myocardial infarction, mortality, mobility, or everyday well-being. The next questions are which population was studied and how long participants were followed. A change on the scale answers one question. Evidence that a drug prolongs life requires mortality data and measures of physical function.