A FormBlends network publication

CagriSema (cagrilintide and semaglutide): the amylin combination (investigational)

Novo Nordisk's once-weekly co-administration of the amylin analogue cagrilintide 2.4 mg with semaglutide 2.4 mg: what amylin adds, REDEFINE 1 and REDEFINE 2 numbers, and how it compares with semaglutide alone. Not FDA approved.

By FormBlends editorial teamUpdated September 4, 2026Educational, not medical advice

CagriSema is Novo Nordisk's answer to the multi-receptor peptides from Lilly and others. Rather than build one molecule that hits several receptors, it pairs the company's existing GLP-1, semaglutide at 2.4 mg, with a new long-acting analogue of amylin, cagrilintide, also at 2.4 mg, given together once a week.

Mechanism and receptor profile

Two active peptides. Semaglutide is a GLP-1 receptor agonist (94% homology to human GLP-1, per the Ozempic label). Cagrilintide is an analogue of amylin, the beta-cell hormone co-secreted with insulin, which acts on amylin receptors to slow gastric emptying and reduce food intake through a central pathway distinct from GLP-1's. The trials describe the product as co-administered cagrilintide and semaglutide. No label exists, so there is no FDA-reviewed statement of mechanism.

Regulatory status

No application in Drugs@FDA as of 4 September 2026. The REDEFINE phase 3 program published its first two trials in the New England Journal of Medicine in June 2025 and a comparison against semaglutide alone in 2026.

Trials and their numbers

Headline results from the abstracts
TrialPopulation and durationResultPubMed
REDEFINE 13,417 adults with obesity or overweight plus a weight-related condition, no diabetes; 68 weeksWeight -20.4% with cagrilintide-semaglutide vs -3.0% placebo (difference -17.3 points, 95% CI -18.1 to -16.6); more participants reached 5%, 20%, 25% and 30% thresholds; gastrointestinal events 79.6% vs 39.9%40544433
REDEFINE 21,206 adults with obesity or overweight and type 2 diabetes; 68 weeksWeight -13.7% vs -3.4% (difference -10.4 points, 95% CI -11.2 to -9.5); HbA1c 6.5% or lower in 73.5% vs 15.9%; gastrointestinal events 72.5% vs 34.4%40544432

REDEFINE 1 randomized 2,108 to the combination, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo, so the single-agent arms were small relative to the combination arm. The 2026 Lancet Diabetes and Endocrinology paper is the direct comparison against semaglutide alone; its numbers belong in a trial digest rather than here, and the Research site covers the REDEFINE program.

Adverse events

No label table. From the abstracts: gastrointestinal events (nausea, vomiting, diarrhea, constipation, abdominal pain) in 79.6% against 39.9% on placebo in REDEFINE 1, mainly transient and mild to moderate; 72.5% against 34.4% in REDEFINE 2.

Boxed warning

None; no label exists. Semaglutide's own boxed warning would apply to the semaglutide component if a combination were approved; whether an amylin analogue carries any additional warning is for the review to decide.

Manufacturer

Novo Nordisk funded both trials.

Where next

The semaglutide injection entry has the single-agent baseline (STEP 1, STEP UP at 7.2 mg). The glossary defines amylin and co-formulation.

Questions people ask

What is amylin and why combine it with a GLP-1?

Amylin is a hormone released with insulin from the pancreatic beta cell. It slows gastric emptying and reduces food intake through receptors in the brainstem, a pathway separate from GLP-1's. Cagrilintide is a long-acting amylin analogue; pairing it with semaglutide is meant to add a second appetite signal rather than push one receptor harder.

Did CagriSema beat semaglutide alone?

REDEFINE 1 randomized participants to the combination, semaglutide alone, cagrilintide alone or placebo. The abstract reports the combination at minus 20.4% against minus 3.0% for placebo; the single-agent arm results are in the full paper. Semaglutide 2.4 mg alone produced minus 14.9% in STEP 1, a different trial.

Canonical URL: https://formblendsglp1s.com/agents/cagrisema. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.