The next weight-loss jab targets amylin, a different hormone entirely

GLP-1 drugs have transformed obesity treatment, but they are not the only hormonal lever available. Cagrilintide is a once-weekly agonist of the amylin receptor, a satiety pathway distinct from GLP-1, and CagriSema pairs it with semaglutide in a fixed-dose combination. If amylin agonism adds meaningful weight loss or metabolic benefit, it widens the pharmacological toolkit for adults with overweight or obesity, a major global health challenge. This review pooled the randomised evidence for both approaches against placebo.

The authors searched four databases from inception to March 2026 for randomised controlled trials testing cagrilintide monotherapy or CagriSema against placebo in adults with overweight or obesity. Four trials totalling 5425 participants qualified. Outcomes included percentage and absolute body weight change, waist circumference, blood pressure, HbA1c and adverse events, pooled with random-effects models and expressed as mean differences or risk ratios.

Cagrilintide alone cut body weight by 6.08% (5.89 kg) versus placebo and lowered blood pressure, but produced no meaningful improvement in HbA1c. CagriSema reduced weight by 5.98% (4.68 kg), trimmed waist circumference by 10.91 cm, and lowered both systolic blood pressure and HbA1c, adding a glycaemic benefit the monotherapy lacked. Both treatments carried modest but statistically significant increases in adverse events, and results varied substantially between trials on most outcomes.

The findings position amylin agonism as a credible second pillar of obesity pharmacotherapy alongside the GLP-1 class, with the combination offering broader cardiometabolic effects than cagrilintide alone. The evidence base is still thin, though: four trials, substantial variation between them, and no long-term data on durability. The authors call for larger and longer trials to confirm efficacy and safety, and head-to-head comparisons against established weight-loss therapies remain to be done.

If you follow the weight-loss drug story, this is the next chapter to watch: a second appetite hormone, amylin, is now backed by pooled randomised evidence for meaningful weight loss, both alone and combined with semaglutide. The trade-offs look familiar, with more adverse events than placebo and open questions about long-term use. Nothing here changes what anyone should do today, but it signals where obesity treatment is heading.