Cagrilintide: The Amylin Half of CagriSema
A weekly amylin receptor agonist with a C20 fatty diacid linker. Pairs with semaglutide as CagriSema, producing the highest weight loss of any GLP-1-class therapy submitted to the FDA so far.
How It Works
Cagrilintide binds the amylin receptor (AMY-R) and the related calcitonin receptor. Amylin is co-secreted with insulin from pancreatic β-cells and signals satiety to the brainstem.
Amylin pathway slows stomach emptying via vagal signaling — similar effect to GLP-1, but through a different receptor. Combining the two stacks the satiety signal.
Acts on amylin receptors in the area postrema and hypothalamus to suppress appetite. The non-GLP-1 pathway is why CagriSema beats semaglutide alone — it pulls a different lever.
Same lipidation strategy as semaglutide and tirzepatide. Albumin binding extends half-life to ~7 days, enabling once-weekly subcutaneous injection.
What the Data Shows
Daily Dosing Schedule
Key Takeaways
- 20.4% mean weight loss at 68 weeks with CagriSema in non-diabetics (REDEFINE 1, NEJM 2025) — slightly above tirzepatide.
- 13.7% mean weight loss in T2D patients (REDEFINE 2) — roughly double placebo.
- Cagrilintide alone produces ~11.5% loss — competitive with semaglutide monotherapy.
- Novo Nordisk submitted CagriSema to FDA in December 2025; potential 2026 approval.
- Amylin and GLP-1 pathways are pharmacologically distinct, which is why combining them adds rather than overlaps benefit.
- GI adverse-event rate ~80% in trials — driven mostly by the semaglutide component.
- Long-term (>2 yr) durability of the additive amylin+GLP-1 effect.
- Whether cagrilintide monotherapy will ever be marketed separately from semaglutide.
- Head-to-head CagriSema vs retatrutide outcomes (no direct comparison trial yet).
- Optimal dose ratio when neither component is at its maximum.
- Cardiovascular outcomes trial data (REDEFINE-CVOT ongoing).
Frequently Asked Questions
What is cagrilintide?
Cagrilintide is a long-acting amylin analog developed by Novo Nordisk. It is a 37-amino-acid peptide with a C20 fatty diacid linker giving it a 7-day half-life for once-weekly subcutaneous injection. Cagrilintide is rarely used alone — its main role is as the amylin half of CagriSema, paired with semaglutide.
What is CagriSema?
CagriSema is the fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) in a single weekly injection. In the REDEFINE 1 trial, it produced 20.4% mean weight loss at 68 weeks — slightly more than tirzepatide and dramatically more than semaglutide alone (14.9%).
How does cagrilintide differ from GLP-1 drugs?
Cagrilintide acts on amylin receptors, not GLP-1 receptors. Amylin is a separate satiety hormone co-secreted with insulin from pancreatic β-cells. The two pathways are pharmacologically independent, which is why combining them adds weight-loss benefit rather than just doubling the dose of one mechanism.
When will CagriSema be FDA-approved?
Novo Nordisk submitted CagriSema to the FDA for chronic weight management in December 2025, supported by the REDEFINE 1 and REDEFINE 2 Phase 3 trials. Standard FDA review is ~10 months, putting potential approval in late 2026. No firm date is published yet.
How does CagriSema compare to retatrutide?
No head-to-head trial exists. CagriSema produced 20.4% loss at 68 weeks in REDEFINE 1; retatrutide produced 22.8% at 48 weeks in TRIUMPH-1 (different durations make direct comparison imperfect). Both meaningfully exceed tirzepatide (~21% in SURMOUNT-1 at 72 weeks).
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