Combining Amylin Analogue Cagrilintide With Semaglutide Produces 17% Weight Loss in 20 Weeks
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 17.1% weight loss in 20 weeks Cagrilintide 2.4 mg added to semaglutide 2.4 mg produced 17.1% body weight reduction — 7.4% more than semaglutide with placebo
- Evidence Grade:
- 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.
- Study Age:
- 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.
- Original Title:
- 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.
- Published In:
- Lancet (London, England), 397(10286), 1736-1748 (2021)
- Authors:
- Enebo, Lone B, Berthelsen, Kasper K, Kankam, Martin, Lund, Michael T, Rubino, Domenica M, Satylganova, Altynai, Lau, David C W
- Database ID:
- RPEP-05367
Evidence Hierarchy
Frequently Asked Questions
What is cagrilintide and how is it different from semaglutide?
Cagrilintide is a long-acting analogue of amylin, a hormone released after meals that signals fullness. Semaglutide mimics GLP-1, a different satiety hormone. Combining both targets two complementary appetite pathways for greater weight loss than either alone.
When will CagriSema be available?
As of this study (2021), CagriSema was in early clinical development. Novo Nordisk has since advanced it to Phase 3 trials. If results are positive and regulatory approval is granted, it could become available within a few years.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-05367APA
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
MLA
Enebo, Lone B, et al. "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, 2021. https://doi.org/10.1016/S0140-6736(21)00845-X
RethinkPeptides
RethinkPeptides Research Database. "Safety, tolerability, pharmacokinetics, and pharmacodynamics..." RPEP-05367. Retrieved from https://rethinkpeptides.com/research/enebo-2021-safety-tolerability-pharmacokinetics-and
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.