# Cagrilintide - Canonical: https://residue.info/c/cagrilintide/ - Also called: NN9838, AM833, CagriSema (with semaglutide) - Evidence grade: B (Randomized human trials). Randomized phase 2 and phase 3 (REDEFINE) trials are published in The Lancet and NEJM; Drugs@FDA lists no approved application. - Status: Investigational — not FDA-approved - PubChem CID: 171397054 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Cagrilintide is an investigational long-acting amylin analog given once weekly by injection. Alone, it reduced body weight by 6.0–10.8% versus 3.0% with placebo in a phase 2 trial [1]. Combined with semaglutide 2.4 mg as CagriSema, weight fell 20.4% versus 3.0% over 68 weeks in the phase 3 REDEFINE 1 trial [2]. It is not FDA-approved. ## Key findings - Phase 2 (706 participants randomized to cagrilintide): weight reduction of 6.0–10.8% across 0.3–4.5 mg doses versus 3.0% with placebo; the 4.5 mg dose beat liraglutide 3.0 mg (10.8% vs 9.0%) [1]. (anchor: https://residue.info/c/cagrilintide/#kf-pmid-34798060) - REDEFINE 1 (3,417 adults with overweight or obesity): cagrilintide–semaglutide produced −20.4% versus −3.0% at 68 weeks [2]. (anchor: https://residue.info/c/cagrilintide/#kf-pmid-40544433) - REDEFINE 2 (1,206 adults with type 2 diabetes): −13.7% versus −3.4%, with 73.5% reaching HbA1c ≤6.5% versus 15.9% [3]. (anchor: https://residue.info/c/cagrilintide/#kf-pmid-40544432) - Gastrointestinal adverse events affected 79.6% on cagrilintide–semaglutide versus 39.9% on placebo in REDEFINE 1, mainly transient and mild to moderate [2]. (anchor: https://residue.info/c/cagrilintide/#kf-pmid-40544433-2) - Cagrilintide's half-life was 159–195 hours in the phase 1b trial, and it did not alter semaglutide exposure [4]. (anchor: https://residue.info/c/cagrilintide/#kf-pmid-33894838) ## Effects by system - Body weight (alone) (grade B): 6.0–10.8% reduction at 26 weeks across doses versus 3.0% placebo [1]. (anchor: https://residue.info/c/cagrilintide/#effect-body-weight-alone) - Body weight (with semaglutide) (grade B): −20.4% at 68 weeks in REDEFINE 1 [2]; −13.7% in type 2 diabetes [3]. (anchor: https://residue.info/c/cagrilintide/#effect-body-weight-with-semaglutide) - Glycemic control (grade B): In a 32-week phase 2 diabetes trial, CagriSema lowered HbA1c by 2.2 points versus 1.8 with semaglutide (difference not significant) and 0.9 with cagrilintide alone [5]. (anchor: https://residue.info/c/cagrilintide/#effect-glycemic-control) - Gastrointestinal (adverse) (grade B): GI events 41–63% versus 32% with placebo for cagrilintide alone, mainly nausea [1]. (anchor: https://residue.info/c/cagrilintide/#effect-gastrointestinal-adverse) ## How does Cagrilintide work? Amylin is a peptide hormone co-secreted with insulin by pancreatic beta cells. Cagrilintide is a long-acting amylin analog designed for once-weekly dosing; its development rationale is a mechanism distinct from, and complementary to, GLP-1 receptor agonism [1]. The phase 1b trial showed cagrilintide exposure rose in proportion to dose without changing semaglutide's exposure or elimination, which is what made a fixed-dose combination feasible [4]. ## How long does Cagrilintide last in the body? In the phase 1b trial in 96 people with overweight or obesity, cagrilintide (0.16–4.5 mg) had a half-life of 159–195 hours and a median time to peak of 24–72 hours. Semaglutide 2.4 mg given alongside had a half-life of 145–165 hours [4]. ## What did the clinical trials find? **Cagrilintide alone.** A Lancet phase 2 dose-finding trial randomized 706 participants to five doses of cagrilintide (0.3–4.5 mg), 99 to liraglutide 3.0 mg and 101 to placebo. Weight fell 6.0–10.8% (6.4–11.5 kg) with cagrilintide against 3.0% with placebo, and the top dose produced more weight loss than liraglutide (10.8% versus 9.0%). Discontinuation was similar across groups, at 10% overall [1]. **CagriSema in type 2 diabetes (phase 2).** In 92 participants over 32 weeks, weight fell 15.6% with CagriSema versus 5.1% with semaglutide and 8.1% with cagrilintide. HbA1c fell 2.2 points with CagriSema and 1.8 with semaglutide, a difference that did not reach statistical significance (p=0.075). Time in glucose range rose to 88.9% with CagriSema [5]. **REDEFINE 1.** In 3,417 adults with overweight or obesity, 2,108 were assigned to cagrilintide–semaglutide and 705 to placebo, with smaller single-agent arms. Mean weight change at 68 weeks was −20.4% versus −3.0% (difference −17.3 points) [2]. **REDEFINE 2.** In 1,206 adults with obesity and type 2 diabetes, weight change was −13.7% versus −3.4%, and 73.5% versus 15.9% reached an HbA1c of 6.5% or less [3]. ## What adverse events were reported in trials? Gastrointestinal events dominate. With cagrilintide alone, 41–63% of participants had gastrointestinal events versus 32% with placebo, mostly nausea (20–47% versus 18%), and administration-site reactions were also common [1]. In REDEFINE 1, gastrointestinal events affected 79.6% on the combination versus 39.9% on placebo [2]; in REDEFINE 2 the figures were 72.5% versus 34.4% [3]. Most were transient and mild to moderate. Cagrilintide has no approved application in Drugs@FDA, alone or in combination, and does not appear on FDA's compounding category lists. Any product sold as "cagrilintide" outside a trial is not an approved drug. ## What is still unknown? - **Single-agent arms in phase 3.** REDEFINE 1 included cagrilintide-only and semaglutide-only groups [2]; comparisons among them deserve close reading of the full paper. - **Long-term safety and outcomes** beyond 68 weeks are being studied in registered trials [6]. ## Frequently asked questions **What is CagriSema?** CagriSema is the investigational once-weekly co-administration of cagrilintide 2.4 mg and semaglutide 2.4 mg [3]. In REDEFINE 1 it reduced body weight by 20.4% versus 3.0% with placebo at 68 weeks [2]. **Is cagrilintide FDA-approved?** No. At our last fetch, openFDA Drugs@FDA returned no application for cagrilintide. Phase 3 trials are active or recruiting on ClinicalTrials.gov [6]. **What are the side effects of cagrilintide?** The most frequent were gastrointestinal (nausea, constipation, diarrhea) and injection-site reactions. Gastrointestinal events affected 41–63% on cagrilintide versus 32% on placebo, primarily nausea [1]. **How long does cagrilintide last in the body?** In a phase 1b study its half-life ranged from 159 to 195 hours (about 7–8 days), with peak levels 24–72 hours after injection [4]. **How does cagrilintide compare with semaglutide?** In a small phase 2 diabetes trial, cagrilintide alone reduced weight by 8.1% and semaglutide alone by 5.1% at 32 weeks, while the combination reduced it by 15.6% [5]. See our cagrilintide vs semaglutide comparison. **What is cagrilintide?** Cagrilintide is an investigational long-acting amylin analog given once weekly. Alone it reduced weight by 6.0–10.8% in phase 2 [1]; with semaglutide 2.4 mg as CagriSema it reduced weight by 20.4% in REDEFINE 1 [2]. It is not FDA-approved. ## Sources [1] 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 et al. Lancet. 2021. https://pubmed.ncbi.nlm.nih.gov/34798060/ [2] Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT et al. N Engl J Med. 2025. https://pubmed.ncbi.nlm.nih.gov/40544433/ [3] Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. Davies MJ et al. N Engl J Med. 2025. https://pubmed.ncbi.nlm.nih.gov/40544432/ [4] 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 et al. Lancet. 2021. https://pubmed.ncbi.nlm.nih.gov/33894838/ [5] Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias JP et al. Lancet. 2023. https://pubmed.ncbi.nlm.nih.gov/37364590/ [6] ClinicalTrials.gov registry search: cagrilintide OR CagriSema. 44 registered studies at fetch. https://clinicaltrials.gov/search?intr=cagrilintide%20OR%20CagriSema --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.