CagrilintideWhat the studies show

The dose-finding trial was published in The Lancet in 2021. It enrolled 706 adults with obesity, or overweight plus a weight-related condition, and randomised them to placebo, to one of five weekly doses of cagrilintide from 0.3 to 4.5 mg, or to liraglutide 3 mg, an approved GLP-1 drug, for 26 weeks ¹. Weight loss rose with the dose: from 6.0% at 0.3 mg to 10.8% at 4.5 mg, against 3.0% on placebo and 9.0% on liraglutide ¹. At the top dose, cagrilintide edged out liraglutide — the first time an amylin analogue had matched a GLP-1 drug head to head.

The combination is where the programme went. A phase 1b trial of 96 people, published alongside the phase 2 trial, found that adding cagrilintide to semaglutide 2.4 mg roughly doubled the weight loss at 20 weeks: 17.1% at the highest cagrilintide dose against 9.8% for semaglutide with placebo ². A phase 2 trial in 92 people with type 2 diabetes, published in The Lancet in 2023, found 15.6% weight loss on the combination at 32 weeks against 5.1% on semaglutide alone and 8.1% on cagrilintide alone, with HbA1c down 2.2 percentage points ³.

The phase 3 REDEFINE 1 trial reported in 2025. In 3,417 adults with obesity or overweight and no diabetes, CagriSema produced an average 20.4% weight loss at 68 weeks against 3.0% on placebo, 11.8% on cagrilintide alone and 14.9% on semaglutide alone ⁴. A substantial share of participants did not stay on the full dose, which the investigators noted when the result came in below what the phase 2 numbers had suggested; it was still among the largest results reported in a phase 3 obesity trial ⁴.

Nausea, vomiting, constipation and reduced appetite were the common complaints with cagrilintide alone, mostly mild to moderate and most frequent in the first weeks; injection-site reactions were more common than with liraglutide ¹. In the small combination trials, gastrointestinal side effects looked similar in frequency to semaglutide alone ². In REDEFINE 1 they were more frequent on CagriSema than on placebo, and more participants stopped because of them ⁴.

Cagrilintide has no approval, no safety record outside trials, and no outcomes data: nothing yet on heart attacks, strokes, or what happens when it is stopped. The amylin class has one approved member, pramlintide, a short-acting injection approved in the U.S. for diabetes, which says something about the receptor and little about a weekly drug given for weight. The rest of the phase 3 programme was still running as of this writing, and a regulator has not yet reviewed any of it.