Combining cagrilintide (a long-acting amylin analogue) with semaglutide 2.4 mg achieved 17.1% body weight loss in 20 weeks — 7.4% more than semaglutide with placebo — with an acceptable safety profile.
17.1% weight loss in 20 weeksCagrilintide 2.4 mg added to semaglutide 2.4 mg produced 17.1% body weight reduction — 7.4% more than semaglutide with placebo
What the researchers found
Cagrilintide 2.4 mg plus semaglutide 2.4 mg achieved 17.1% body weight reduction at 20 weeks, with an estimated treatment difference of -7.4% versus semaglutide plus placebo (95% CI -11.2 to -3.5). No pharmacokinetic interactions between the drugs.
Why it matters
This trial established that combining two appetite-regulating peptide hormones is safe and produces substantially greater weight loss than either alone, laying the groundwork for CagriSema as a next-generation obesity treatment.
The numbers in context
96 randomized; 17.1% weight loss at cagrilintide 2.4mg; 15.7% at 1.2mg; 15.4% at 4.5mg; 9.8% placebo; treatment difference -7.4%; 37% GI AEs; cagrilintide t1/2 159-195h; semaglutide t1/2 145-165h
How the study worked
Randomized, double-blind, placebo-controlled, multiple-ascending dose Phase 1b trial. Six sequential cohorts at a single US center. 96 randomized (95 treated). Cagrilintide 0.16-4.5 mg or placebo co-escalated with semaglutide 2.4 mg over 16 weeks, target dose maintained 4 weeks, 5-week follow-up.
Who was studied
Adults aged 18-55, BMI 27.0-39.9, otherwise healthy
What this study cannot tell us
Small Phase 1b trial (96 participants) designed primarily for safety, not efficacy. Only 20 weeks of treatment — insufficient to assess long-term weight loss plateau. No lifestyle intervention included. Participants were otherwise healthy, so results may differ in people with obesity-related conditions.
How to read the evidence
Moderate evidence: randomized, double-blind, placebo-controlled design published in Lancet, but small sample size (96) and short duration (20 weeks) as expected for Phase 1b.
When this study was published
Published in 2021. CagriSema has since advanced to Phase 3 trials with results expected in 2024-2025, and Novo Nordisk plans to submit for regulatory approval.
The bigger picture
CagriSema represents the trend toward combination peptide therapies for obesity. By targeting both GLP-1 and amylin pathways simultaneously, it may achieve weight loss approaching surgical levels. This Phase 1b data set the stage for larger Phase 3 trials now underway.
Questions still open
- Will the combination maintain its weight loss advantage over longer treatment periods in larger trials?
- How does CagriSema compare to tirzepatide for weight management?
- Could the amylin + GLP-1 combination benefit patients who plateau on semaglutide alone?
Common questions
What is cagrilintide and how is it different from semaglutide?
When will CagriSema be available?
Read the original research
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.
Lancet (London, England), 397(10286), 1736-1748
Citation
Enebo, Lone B; Berthelsen, Kasper K; Kankam, Martin; Lund, Michael T; Rubino, Domenica M; Satylganova, Altynai; Lau, David C W. (2021). 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.. Lancet (London, England), 397(10286), 1736-1748. https://doi.org/10.1016/S0140-6736(21)00845-X