Also known as AM833. Long-acting acylated amylin analogue (amylin receptor agonist) developed by Novo Nordisk. Half-life approximately 7 days enabling once-weekly subcutaneous dosing. In Phase 3 REDEFINE trials as CagriSema (combined with semaglutide 2.4 mg). Not FDA approved as of May 2026.
Cagrilintide binds the calcitonin receptor (CTR) complexed with receptor activity-modifying proteins RAMP1 and RAMP3, forming amylin receptors expressed densely in the area postrema, nucleus accumbens, and dorsal vagal complex. This produces satiety signaling, reduced food intake, and delayed gastric emptying — mechanisms that are anatomically and molecularly distinct from GLP-1 receptor agonism, making them additive when combined.[1]
Like semaglutide, cagrilintide carries a C18 fatty diacid side chain attached via a linker to its peptide backbone. This modification enables tight non-covalent binding to serum albumin, dramatically extending the half-life from native amylin's ~4 minutes to approximately 7 days. Albumin's long circulatory lifespan (via FcRn recycling) is effectively co-opted to sustain cagrilintide exposure, enabling once-weekly subcutaneous dosing in the clinical setting.[1]
Combining cagrilintide (amylin receptor agonist) with semaglutide (GLP-1R agonist) targets two distinct receptor systems governing energy homeostasis. Phase 2 data suggested additive weight loss exceeding either agent alone at matched doses. The REDEFINE program evaluates CagriSema 2.4 mg/2.4 mg once weekly. REDEFINE 1 Phase 3 data (Novo Nordisk 2024) reported approximately 22.7% weight reduction at 68 weeks versus approximately 8% with placebo — exceeding semaglutide 2.4 mg alone (~15% in STEP 1).[2]
Model your plasma concentration curve in real time · Visualize when doses overlap · Free iOS app
Most sources cite only plasma half-life. Halflife Labs' approach separates three distinct timescales for a complete pharmacokinetic picture:
| Layer | Metric | Value (SC) | Source |
|---|---|---|---|
| 1 | Plasma half-life | ~7 days | Lau et al. Lancet 2021, PMID 34562347 (human Phase 1/2) |
| 2 | Near-complete clearance (5 × t½) | ~35 days | Derived from reported t½ using standard 5-half-life rule |
| 3 | Satiety / weight recovery post-discontinuation | Weeks (amylin axis recovery) | Clinical observation; no published washout data |
Based on a plasma half-life of ~7 days, the approximate percent of drug remaining at each interval post-last dose:
| Route | Available | Data Status | Notes |
|---|---|---|---|
| SC injection | Yes | Human Phase 2 (Lancet 2021) | Once-weekly; doses 0.25–4.5 mg studied |
| IV | Research only | Preclinical / early PK | Not used clinically |
| IM | No | No published data | — |
| Oral | No | No published data | Peptide; not orally bioavailable without absorption enhancer |
| Compound | Class | Half-Life | Status | Route |
|---|---|---|---|---|
| Cagrilintide | Amylin analogue | ~7 days | Phase 3 | SC |
| Semaglutide | GLP-1R agonist | ~7 days | FDA approved (Ozempic / Wegovy) | SC / oral |
| Retatrutide | Triple GLP-1/GIP/GCG | ~6 days | Phase 3 | SC |
| Pramlintide | Short-acting amylin | ~48 min | FDA approved (Symlin) | SC (with meals) |
Gastrointestinal adverse effects — nausea, vomiting, decreased appetite, and diarrhea — are the most common reported events, similar in character to the GLP-1 class. Early Phase 3 data suggest that nausea incidence with CagriSema combination may be modestly higher than with semaglutide 2.4 mg alone, particularly during dose escalation.[2]
Unlike GLP-1R agonists (semaglutide, liraglutide), cagrilintide does not act at the GLP-1 receptor and carries no theoretical concern for thyroid C-cell tumors attributable to that receptor class. Long-term safety data from REDEFINE trials are not yet fully published as of May 2026.
Approximately 7 days (168 hours) following subcutaneous injection, based on human Phase 1/2 pharmacokinetic data from the Lancet 2021 dose-finding trial. Source: Lau DCW et al. Lancet 2021;398(10300):576–588. PMID 34562347.
CagriSema is a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg administered once weekly by subcutaneous injection. It targets two distinct receptor systems (amylin and GLP-1R) simultaneously. It is being evaluated in the Phase 3 REDEFINE program (e.g., NCT05567796) for chronic weight management.
Cagrilintide is an amylin receptor agonist. It binds calcitonin receptor (CTR) complexed with RAMP1 and RAMP3 proteins in brain regions governing appetite (area postrema, nucleus accumbens, dorsal vagal complex). This reduces food intake, delays gastric emptying, and suppresses glucagon — mechanisms that are complementary and additive to GLP-1 receptor agonism.
No. As of May 2026, cagrilintide and CagriSema are investigational and not FDA approved. Phase 3 REDEFINE trials are ongoing. Novo Nordisk has not yet received regulatory approval for this compound in any indication.
In the Phase 2 Lancet 2021 trial, the highest dose studied (4.5 mg once weekly SC) produced approximately 10.8% body weight loss at 26 weeks compared to placebo. Lower doses produced proportionally less weight loss. Source: Lau DCW et al. Lancet 2021, PMID 34562347.
REDEFINE 1 Phase 3 data (Novo Nordisk 2024, NCT05567796): approximately 22.7% body weight loss at 68 weeks with CagriSema 2.4 mg/2.4 mg weekly, versus approximately 8% with placebo. This substantially exceeds semaglutide 2.4 mg alone (~15% in STEP 1) and represents one of the largest weight reductions reported in any Phase 3 obesity trial.
Pramlintide (Symlin) is an unmodified amylin analogue with a plasma half-life of approximately 48 minutes, requiring injection before each meal (up to 3x daily). Cagrilintide is a next-generation acylated amylin analogue engineered with a C18 fatty diacid chain enabling albumin binding, extending the half-life to approximately 7 days and enabling once-weekly dosing — analogous to how semaglutide improved on earlier GLP-1R agonists.
Approximately 4–5 weeks with once-weekly subcutaneous dosing, corresponding to 4–5 half-lives of approximately 7 days each. At steady state, plasma concentrations are approximately 2–3-fold higher than after the first dose, consistent with accumulation during the buildup period.
The Halflife app models cagrilintide concentration curves, dose overlap, and washout timelines — all on-device, no account required.