Cagrilintide
Cagrilintide (AM833 / NNC0174-0833 / NN9838), a long-acting acylated amylin analogue [PMID 34288673; ClinicalTrials.gov orgStudyIdInfo NN9838-4942]
Investigational once-weekly long-acting amylin receptor agonist developed by Novo Nordisk for obesity and type 2 diabetes. Phase 3 RCTs show 11.5-11.8% weight loss as monotherapy and 13.7-22.7% as CagriSema (cagrilintide plus semaglutide). Phase 2 monotherapy produced 6.0-10.8% weight loss at 26 weeks, superior to liraglutide 3.0 mg at the highest dose [PMID 34798060; PMID 40544433; PMID 40544432].
Last updated: 2026-03-10
Safety Summary
In Phase 2 (NCT03856047): nausea 20-47% cagrilintide versus 18% placebo; constipation 8-21% versus 7%; diarrhea 7-18% versus 9%; vomiting 5-9% versus 3%; injection-site reactions 4-12% versus 0% [NCT03856047; PMID 34798060]. In Phase 2 T2D trial: mostly mild-moderate GI events; no level 2 or 3 hypoglycemia reported [PMID 37364590]. REDEFINE 1: GI events 79.6% CagriSema versus 39.9% placebo, mainly transient and mild-moderate [PMID 40544433]. REDEFINE 2: GI events 72.5% CagriSema versus 34.4% placebo [PMID 40544432]. Discontinuation due to AEs 6-8.4% in Phase 3 [EXA-a8d6b91aca40]. Hypotension reported in 1.8% CagriSema versus 0.4% placebo in REDEFINE 1 BP analysis [PMID 41328546]. Meta-analysis of 4 RCTs confirmed GI AEs more frequent with CagriSema (RR 1.32) [PMID 41759565].
Known Side Effects
20-47% (vs 18% placebo in Phase 2)
8-21% (vs 7% placebo)
7-18% (vs 9% placebo)
5-9% (vs 3% placebo)
4-12% (vs 0% placebo)
Common (included in GI category)
Common (pharmacological effect)
Who Should NOT Use This
Talk to Your Doctor
Before considering Cagrilintide, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-10]
Evidence Assessment
Phase 3a data published in peer-reviewed journals (NEJM 2025). REDEFINE 1 (PMID 40544433, N=3417) included a cagrilintide monotherapy arm (N=302) showing -11.5% weight loss at 68 weeks. REDEFINE 2 (PMID 40544432, N=1206) published Phase 3a combination data. A Phase 2 monotherapy RCT (PMID 34798060, N=706) and Phase 2 T2D RCT (PMID 37364590, N=92) provide additional human evidence. Meta-analysis of 4 RCTs (PMID 41759565, N=4419) confirms efficacy. Dedicated Phase 3 monotherapy registration trials (RENEW: NCT07220642, NCT07220759) are ongoing but not yet published. Not FDA-approved.
1Development of Cagrilintide, a Long-Acting Amylin AnaloguePMID 34288673
Kruse T, Hansen JL, Dahl K, et al. - Journal of Medicinal Chemistry (2021) - Preclinical / Drug Development
Describes the design and selection of cagrilintide as a stable, lipidated long-acting amylin analogue for obesity. Reports structure-activity optimization and selection for clinical development.
Limitations: Only abstract available in source set. Industry-authored (Novo Nordisk). Sequence-level detail not available from abstract alone.
2Safety, tolerability, PK, and PD of cagrilintide with semaglutide 2.4 mgPMID 33894838
Enebo LB, Berthelsen KK, Kankam M, et al. - Lancet (2021) - Phase 1b RCT - 95
Cagrilintide 2.4 mg plus semaglutide 2.4 mg: -17.1% (SE 1.5) versus placebo plus semaglutide: -9.8% (SE 1.2); ETD -7.4% (95% CI -11.2 to -3.5) at 20 weeks. Dose-proportional PK. Half-life 159-195 hours. No PK interaction with semaglutide.
Limitations: Small, single-center, short-duration, combination-only, manufacturer-funded.
3Once-weekly cagrilintide for weight management (Phase 2)PMID 34798060
Lau DCW, Erichsen L, Francisco AM, et al. - Lancet (2021) - Phase 2 RCT - 706
Dose-dependent weight loss of 6.0-10.8% at 26 weeks versus 3.0% placebo. Cagrilintide 4.5 mg superior to liraglutide 3.0 mg (10.8% vs 9.0%, p=0.03). Weight loss progressive without plateau. Nausea 20-47% versus 18% placebo.
Limitations: 26 weeks duration. Excluded diabetes. Industry-funded. Long-term monotherapy durability not established.
4CagriSema in type 2 diabetes (Phase 2)PMID 37364590
Frias JP, Deenadayalan S, Erichsen L, et al. - Lancet (2023) - Phase 2 RCT - 92
CagriSema: -15.6% weight, -2.2 pp HbA1c. Semaglutide: -5.1% weight, -1.8 pp HbA1c. Cagrilintide: -8.1% weight, -0.9 pp HbA1c. SBP: CagriSema -13 mmHg versus cagrilintide -3 versus semaglutide +1. CGM TIR 88.9% CagriSema. No level 2/3 hypoglycemia. No fatal AEs.
Limitations: Small (N=92), Phase 2, metformin-based, manufacturer-funded. Duration 32 weeks.
5Thorough QT study of cagrilintidePMID 39279639
Gabe MBN, et al. - Diabetes, Obesity and Metabolism (2024) - QT Safety Study - 105
No clinically relevant QTc prolongation at doses up to 4.5 mg. Upper bounds of 90% CI for placebo-adjusted QTcF change stayed below 10 ms at all time points.
Limitations: Healthy-volunteer safety study, not efficacy study. Manufacturer-funded.
6CagriSema in adults with overweight or obesity (REDEFINE 1)PMID 40544433
Garvey WT, Bluher M, Osorto Contreras CK, et al. - New England Journal of Medicine (2025) - Phase 3a RCT - 3417
CagriSema -20.4% weight loss at 68 weeks versus -3.0% placebo (treatment-policy estimand). Monotherapy arms: semaglutide -14.9%, cagrilintide -11.5%. 53.6% of CagriSema achieved >=20% weight loss. GI AEs 79.6% CagriSema versus 39.9% placebo, mostly mild-moderate and transient.
Limitations: Primary endpoint was CagriSema versus placebo, not cagrilintide monotherapy. Manufacturer-funded. Monotherapy arms had smaller N (302 each).
7CagriSema in adults with overweight or obesity and T2D (REDEFINE 2)PMID 40544432
Davies MJ, Bajaj HS, Broholm C, et al. - New England Journal of Medicine (2025) - Phase 3a RCT - 1206
CagriSema -13.7% weight versus -3.4% placebo (p<0.001). 73.5% achieved HbA1c <=6.5% versus 15.9%. GI events 72.5% versus 34.4% placebo.
Limitations: Evaluates CagriSema combination, not cagrilintide alone. Manufacturer-funded.
8Blood pressure effects of CagriSema in REDEFINE 1PMID 41328546
Verma S, et al. - Hypertension (2026) - Secondary analysis of Phase 3a RCT - 3417
CagriSema: SBP -10.9 mmHg versus -2.8 placebo (ETD -8.2). DBP -5.4 versus -1.7 (ETD -3.8). 63% reached ACC/AHA BP targets versus 32% placebo. 72% of SBP reduction mediated by weight loss. In resistant hypertension (n=167), 42% reached targets. 39.6% decreased/stopped antihypertensives. Hypotension 1.8% versus 0.4%.
Limitations: Post hoc secondary analysis. Manufacturer-funded.
9Meta-analysis of CagriSema RCTsPMID 41759565
Gadelmawla AF, et al. - American Journal of Cardiology (2026) - Meta-analysis - 4419
4 RCTs pooled. Cohen's d for weight change: -1.38 (95% CI -1.84 to -0.91; I2=94.8%). MD: -11 kg body weight, -9.41 cm waist circumference, -7.06 mmHg SBP. GI AEs RR 1.32.
Limitations: High heterogeneity (I2=94.8%). Included both monotherapy and combination data.
10Amylin analogues for obesity and diabetes (Review)PMID 41747885
Bailey CJ, et al. - Peptides (2026) - Review
Confirms cagrilintide is a dual AMYR/CTR agonist. Discusses emerging evidence for potential therapeutic benefits in fatty liver disease, kidney complications, resistant hypertension.
Limitations: Review article, not primary data.