Cagrilintide
Cagrilintide (Long-Acting Amylin Analogue — AM833)
Evidence & Status
- Moderate Evidence
- Moderate
At a Glance
A long-acting amylin receptor agonist in late-stage clinical development, studied primarily in combination with Semaglutide for obesity and type 2 diabetes. Designed to complement GLP-1 receptor agonism through a distinct but synergistic mechanism.
Plain English
Researchers study Cagrilintide because it activates the amylin receptor with a once-weekly duration well suited for combination with Semaglutide. Scientists are interested in whether combining GLP-1 receptor agonism with amylin receptor activation produces additive benefits on weight loss and glucose control. The combination — called CagriSema — is in Phase III trials and is being closely followed as a potential next stage in the development of combination metabolic pharmacotherapy.
Overview
Cagrilintide is an investigational long-acting amylin analogue. Evidence for cagrilintide monotherapy must remain distinct from evidence for the fixed-dose cagrilintide/semaglutide combination, CagriSema. Neither cagrilintide nor CagriSema is FDA-approved, and trial dose-escalation schedules are not recommendations for clinical use.
Research Summary
A randomized cagrilintide monotherapy study reported weight-loss findings in adults with overweight or obesity. Separate Phase III publications report results for the cagrilintide/semaglutide combination CagriSema in obesity and type 2 diabetes populations. These outcomes must not be attributed to cagrilintide monotherapy, and neither product is FDA-approved.
Research Areas
- Cagrilintide monotherapy weight-management research
- CagriSema combination research
Safety & Risks
Serious Risks
- Thyroid-related safety remains under investigation; a cagrilintide-specific human thyroid C-cell risk has not been established. Established thyroid C-cell tumor warnings for semaglutide-containing products are not attributed here to cagrilintide.
- Pancreatitis remains an unresolved safety question; a cagrilintide-specific human risk has not been established in this record.
Reported Side Effects
- Nausea
- Vomiting
- Decreased appetite
- Diarrhea
- Injection site reactions
Legal Status by Region
- United States
- Investigational; not FDA-approved
- United Kingdom
- Current authorization status not established in this record
- Australia
- Current authorization status not established in this record
- Canada
- Current authorization status not established in this record
Citations & Sources
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial.
Enebo LB, Berthelsen KK, Kankam M, Lund MT, et al. · Lancet · 2021
PMID 33894838 · DOI 10.1016/S0140-6736(21)00845-X
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.
Garvey WT et al. · The New England Journal of Medicine · 2025
PMID 40544433 · DOI 10.1056/NEJMoa2502081
- Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.
Davies MJ et al. · The New England Journal of Medicine · 2025
PMID 40544432 · DOI 10.1056/NEJMoa2502082
- REDEFINE 1 (NCT05567796).
Registry NCT05567796
- REDEFINE 2 (NCT05394519).
Registry NCT05394519
- REDEFINE 3 (NCT05669755).
Registry NCT05669755
- REDEFINE 4 (NCT06131437).
Registry NCT06131437
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.
Lau DCW, Erichsen L, Francisco AM, Satylganova A, et al. · Lancet · 2021
PMID 34798060 · DOI 10.1016/S0140-6736(21)01751-7
- Investigation of Safety and Efficacy of NNC0174-0833 for Weight Management — a Dose Finding Trial.
Registry NCT03856047