Study: Most effective weight-loss drugs come with the most side effects

What are GLP-1 antagonists?

According to the study, the two most effective drugs lead to a weight loss of about 15 percent. One of them is tirzepatide, marketed by the pharmaceutical company Eli Lilly as the weight-loss injection Mounjaro. The other, the authors say, is the drug cagrisema, currently being developed by the competitor Novo Nordisk, which combines the active ingredients semaglutide and cagrilintide.

In comparison, the weight loss achieved by Wegovy, a preparation containing only the active ingredient semaglutide, is lower, at around ten percent. However, semaglutide as a standalone active ingredient, like tirzepatide, is one of the few GLP-1 drugs proven to reduce cardiovascular risks. The authors emphasize this additional benefit as an important factor in medical decision-making.

The most effective active ingredients compared

The review study also aims to support patients and treating physicians in selecting the appropriate drug. Not every weight reduction offsets the individual risks equally; comorbidities—that is, accompanying conditions such as cardiovascular disease—play a central role here.

In parallel to the scientific debate, health authorities are increasingly facing the decision of the extent to which the—rather costly—GLP-1 treatments should be covered by health insurers. Reimbursement models are also being discussed in France. The study authors provide additional data with their evaluation on which political and medical decision-makers can base their decisions.

Costs and reimbursement as a political issue

For clinical practice, the study means that efficacy and tolerability must always be assessed together. Someone who is severely overweight and also carries an elevated cardiovascular risk, for example, may benefit from a drug that addresses both. In patients with a lower starting weight or without the relevant pre-existing conditions, milder active ingredients may be sufficient to reduce the risk of side effects and treatment discontinuation.

Overall, the BMJ publication underscores the need for a differentiated prescribing practice. It shows that the strongest available weight-loss drugs are not automatically the best choice for every patient, and that the choice of active ingredient should be made together with the treating physician.

What the results mean for patients

In the long term, the authors emphasize, further studies are needed to determine more precisely the balance between weight reduction, cardiovascular benefit, and tolerability. The question of how long the drugs must be taken and what consequences discontinuation has also remains unanswered for now.