Cagrilintide: The Amylin Analog Behind CagriSema

Cagrilintide, also called AM833 or NNC0174-0833, imitates the pancreatic hormone amylin, which is released with insulin and helps signal fullness. Novo Nordisk designed it for a long duration that permits once-weekly trial injections. It remains investigational. Its development includes both a standalone program and use as the amylin component of CagriSema.

The molecule engages amylin and calcitonin receptors. The intended effects are increased satiety, delayed stomach emptying and reduced glucagon release after meals, together lowering food intake. These pathways differ from GLP-1 signaling, creating a rationale for complementary action with a GLP-1 drug. A mechanistic rationale does not validate self-stacking separately purchased preparations.

Supporting references: calcitonin receptors; incretin system.

A randomized Phase 2 dose-finding trial followed 706 participants with overweight or obesity without diabetes for 26 weeks. Weekly target arms were 0.3, 0.6, 1.2, 2.4 and 4.5 mg. The highest target produced mean weight reduction of 10.8%, compared with 3.0% for placebo and 9.0% for daily liraglutide 3 mg.

Existing REDEFINE 1 standalone-arm evidence adds a separate 68-week result: 11.8% mean loss versus 2.3% placebo under the adherence-assuming trial-product estimand, or 11.5% versus 3.0% under treatment policy. At least 15% loss occurred in 31.6% versus 4.7% under the trial-product analysis. These are different studies and estimands, not interchangeable percentages. A completed dedicated standalone Phase 3 program and long-term commercial treatment profile are not established by these results.

Supporting references: up to 10.8% weight loss.

Cagrilintide is one molecule; CagriSema pairs it with semaglutide. A Phase 1b combination trial reported 17.1% mean loss at 20 weeks, while REDEFINE 1 reported 20.4% at 68 weeks under treatment policy and 22.7% under its adherence-assuming analysis. Combination outcomes cannot be assigned to cagrilintide alone.

Pramlintide, sold as Symlin, is another amylin analog and is approved as an adjunct to mealtime insulin in type 1 and type 2 diabetes. Its indication and evidence differ from cagrilintide’s. Separate trials reported 14.9% loss with semaglutide 2.4 mg in STEP 1 and 20.9% with tirzepatide 15 mg in SURMOUNT-1; their different populations, durations and designs preclude a simple efficacy ranking. Lilly’s selective once-weekly amylin agonist eloralintide produced approximately 9%–20% dose-dependent loss in a 48-week Phase 2 trial, which likewise cannot be ranked against a 26-week cagrilintide study. Novo also studies amycretin, a single molecule activating GLP-1 and amylin receptors.

Supporting references: combination; FDA-approved as an adjunct to mealtime insulin; 20.4% mean weight loss over 68 weeks; 14.9% shown by semaglutide 2.4 mg; 20.9% shown by tirzepatide 15 mg; 17.1% weight loss at 20 weeks; amycretin, a single-molecule GLP-1 and amylin receptor agonist; selective amylin receptor agonist.

Trial target doses describe controlled research procedures, not an approved consumer regimen. The 26-week monotherapy trial and CagriSema protocols use different contexts; REDEFINE combination research included a 2.4 mg cagrilintide component. Do not convert these targets into instructions for research-vendor material.

Gastrointestinal adverse events, particularly nausea, were the most common events in the 26-week study. Depending on dose, 41%–63% of cagrilintide recipients had a gastrointestinal event versus 32% with placebo. Existing REDEFINE 1 standalone-arm reporting puts nausea-related permanent discontinuation at 1.0% versus 0.1% placebo; that is not an all-adverse-event discontinuation rate.

A 2024 thorough-QT study in 105 healthy participants found no clinically relevant QTcF prolongation at measured time points following the final 4.5 mg dose. This monitored cardiac finding does not establish every aspect of safety. Longer-term monotherapy safety remains limited, and trial averages cannot predict individual tolerance.

Supporting references: no clinically relevant QTcF prolongation.

Cagrilintide is not approved by the FDA or another regulator in the reported regulatory context. FDA states that it is not a component of an approved drug and cannot be used in compounding under federal law. A clinician therefore has no approved or federally permitted compounded cagrilintide product to prescribe under this context; clinical-trial enrollment is the legitimate research-access pathway.

Novo has begun the RENEW 1 standalone Phase 3 trial comparing cagrilintide with placebo. Most late-stage development also involves CagriSema, whose FDA submission is separate from standalone approval. Announced programs and submission timing do not guarantee a launch or final regulatory decision.

Supporting references: started a standalone Phase 3 trial; cannot be used in compounding under federal law; submitted to the FDA for review.