Cagrilintide and CagriSema: What the Published Trials Show
Cagrilintide is an amylin analog studied alone and with semaglutide as CagriSema. Here is what three published trials measured, and what they cannot tell you.
By Peptidelogy Editorial Team, published September 25, 2026. 6 min read.
Medically reviewed by
Valeria Marulanda, FNP-BC
Board-Certified Family Nurse Practitioner
Valeria Marulanda is a board-certified Family Nurse Practitioner (FNP-BC) with a Bachelor of Science in Nursing from Florida Atlantic University and a Master of Science in Nursing from St. Thomas University. Since 2018, she has specialized in medical aesthetics, focusing on face and body treatments. Valeria loves longevity, science-driven skin treatments, and regenerating the human body from the inside out.
Key points
- Cagrilintide is a long-acting analog of amylin, a satiety hormone made in the pancreas. It works through a different pathway from GLP-1 drugs such as semaglutide.
- In a 26-week phase 2 trial that gave cagrilintide to 706 adults without diabetes, mean body weight fell by 6.0% to 10.8% across five dose levels, against 3.0% on placebo.
- Combined with semaglutide as CagriSema, a 68-week phase 3 trial of 3,417 adults reported a 20.4% mean weight reduction against 3.0% on placebo.
- All three trials were funded by Novo Nordisk, lasted months rather than years, and measured weight and safety, not long-term outcomes such as heart disease.
What cagrilintide is
Natural amylin is a pancreatic hormone that promotes satiety. Cagrilintide is a long-acting amylin analog that was under investigation for weight management when the first large trial was published in 2021.
That pathway is separate from the one used by semaglutide, a GLP-1 receptor agonist. The difference is the reason the two are studied together. Our cagrilintide profile covers the mechanism in more detail.
The 2021 phase 2 dose-finding trial
This trial (Lau et al., Lancet 2021) ran at 57 sites in ten countries. It enrolled adults without diabetes who had a body-mass index of at least 30, or at least 27 with hypertension or dyslipidaemia. Of 906 people randomly assigned, 706 received once-weekly cagrilintide at one of five dose levels, 99 received once-daily liraglutide and 101 received placebo. Treatment lasted 26 weeks.
Mean weight reduction was 6.0% to 10.8% across the cagrilintide dose levels, compared with 3.0% on placebo. At the highest dose level, cagrilintide produced a 10.8% reduction against 9.0% for liraglutide, a difference of 1.8 percentage points (p=0.03).
Gastrointestinal events were more common with cagrilintide than with placebo: 41% to 63% against 32%, mostly nausea (20% to 47% against 18%). About 10% of participants permanently stopped treatment, and adverse events accounted for 4% of all participants.
Three of the authors are employees and shareholders of the sponsor, Novo Nordisk, and several others report consulting or advisory ties to it.
CagriSema in type 2 diabetes, 2023
The second trial (Frias et al., Lancet 2023) was small and short. It randomly assigned 92 adults with type 2 diabetes at 17 US sites to CagriSema (31 people), semaglutide (31) or cagrilintide (30) for 32 weeks.
Blood sugar control, measured as HbA1c, improved by 2.2 percentage points with CagriSema, 1.8 with semaglutide and 0.9 with cagrilintide. CagriSema was better than cagrilintide alone, but the gap against semaglutide (0.4 percentage points, 95% CI -0.8 to 0.0, p=0.075) was not statistically significant.
Weight told a different story. Mean change was -15.6% with CagriSema, -5.1% with semaglutide and -8.1% with cagrilintide, and CagriSema was significantly better than both. No level 2 or 3 hypoglycaemia was reported, and gastrointestinal events were mostly mild or moderate.
The useful reading here is the split: in this small trial the combination clearly helped weight, but its advantage for blood sugar over semaglutide alone was not established.
REDEFINE 1, the phase 3 obesity trial, 2025
REDEFINE 1 (Garvey et al., New England Journal of Medicine 2025) randomly assigned 3,417 adults with overweight or obesity: 2,108 to CagriSema, 302 to semaglutide, 302 to cagrilintide and 705 to placebo. At week 68, the estimated mean change in body weight was -20.4% with CagriSema and -3.0% with placebo, a difference of 17.3 percentage points (95% CI 16.6 to 18.1, p<0.001).
More people on CagriSema than on placebo reached weight-loss thresholds of 5%, 20%, 25% and 30% or more. Gastrointestinal adverse events affected 79.6% of the CagriSema group and 39.9% of the placebo group. They were mainly transient and mild to moderate.
The published abstract reports the comparison against placebo. Results for the single-drug arms are in the full paper, which we cite below.
What these trials cannot tell you
Duration is the first limit. The trials ran 26 to 68 weeks. None reported long-term outcomes such as heart attacks, and none can say what happens to weight after treatment stops.
Funding is the second. All three were sponsored by Novo Nordisk, which is normal for drug development but worth knowing when reading the results.
The third is scope. Participants were adults who met specific body-mass and health criteria. The results do not apply to people outside those criteria, and they say nothing about using any of these compounds outside a clinical setting.
Regulatory status also changes. Cagrilintide was an investigational agent when these papers were published, so check current labeling from your regulator rather than relying on a blog post, including this one.
References
- Lau DCW, Erichsen L, Francisco AM, et al. 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. Lancet. 2021;398(10317):2160-2172. PubMed 34798060
- Frias JP, Deenadayalan S, Erichsen L, et al. 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. Lancet. 2023;402(10403):720-730. PubMed 37364590
- Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2025;393(7):635-647. PubMed 40544433
Figures in this article come from the abstracts and records of the papers above.