A long-acting analog of the pancreatic hormone amylin (co-secreted with insulin from beta cells). Cagrilintide reduces appetite, slows gastric emptying, and suppresses glucagon — complementary to GLP-1 agonism. Combined with semaglutide as CagriSema, the combination achieved up to 25% weight loss in trials.
Cagrilintide is a long-acting acylated analog of amylin, a 37-amino-acid peptide hormone that is co-secreted with insulin from pancreatic beta cells after meals. Amylin's natural functions — slowing gastric emptying, suppressing glucagon, and promoting satiety — complement GLP-1's effects through distinct receptor pathways.
The most exciting development is CagriSema — the fixed-dose combination of cagrilintide + semaglutide in a single weekly injection. In the REDEFINE clinical program, CagriSema achieved approximately 25% weight loss — rivaling surgery and potentially superior to any current single-agent therapy.
Cagrilintide works through amylin receptors in the brainstem, while semaglutide works through GLP-1 receptors in the hypothalamus. Because these are anatomically and pharmacologically distinct satiety pathways, combining them produces additive (possibly synergistic) weight loss. This is the same principle that makes combination drug therapy effective in other diseases — targeting multiple points in a pathway produces greater effects than maxing out a single target.
| Pathway | Effect | Significance |
|---|---|---|
| Amylin receptor agonism | Activates AMY1/AMY3 in area postrema | Distinct satiety pathway from GLP-1 |
| Gastric slowing | Reduces gastric emptying rate | Prolongs satiety and reduces postprandial glucose spikes |
| Glucagon suppression | Reduces inappropriate postprandial glucagon | Complements GLP-1-mediated glucagon suppression |
| Additive with GLP-1 | Different brain targets = additive appetite reduction | CagriSema achieves greater weight loss than either agent alone |
| Acylation | Fatty acid conjugation for albumin binding | Extends half-life for once-weekly injection |
| Study | Design | Findings | Level |
|---|---|---|---|
| REDEFINE 1 | Phase III, n=3,417, 68 weeks | CagriSema 2.4mg: ~25% mean body weight loss. Superior to semaglutide 2.4mg alone (~16%). | Level I |
| REDEFINE 2 | Phase III, T2D | Superior HbA1c reduction and weight loss vs semaglutide alone in T2D patients | Level I |
| Cagrilintide monotherapy | Phase II | Cagrilintide alone produced ~10-11% weight loss at highest dose over 26 weeks | Level II |
| CagriSema vs surgery | Indirect comparison | 25% weight loss approaches outcomes of sleeve gastrectomy (~25-30%) | Indirect |
GI side effects: Nausea, vomiting, diarrhea — similar to GLP-1 class. Possibly higher incidence with combination.
Injection site reactions: Some injection site reactions reported with cagrilintide.
Same class warnings: Thyroid C-cell tumor warning, pancreatitis risk, gallbladder disease — same as GLP-1 agonist class.
| Jurisdiction | Status |
|---|---|
| FDA | Not yet approved. NDA submitted 2025 for CagriSema. Decision expected 2025-2026. |
| Novo Nordisk | Developer. Would be next-generation successor to Wegovy. |
| Market impact | If approved, CagriSema could become the most effective obesity medication available |