October 17, 2026 · 2 min read
Cagrilintide and CagriSema: an amylin analogue studied alongside semaglutide
What cagrilintide is, why researchers pair an amylin analogue with a GLP-1 agonist, and what the REDEFINE 1 phase 3 trial reported.
Amylin is a hormone the pancreas releases alongside insulin. Cagrilintide is a long-acting analogue of it. CagriSema is a fixed combination of cagrilintide and semaglutide, a GLP-1 receptor agonist. Both have been through clinical trials, and this is a summary of what has been published.
The idea behind pairing them
Amylin and GLP-1 both promote satiety, but through different receptors and pathways. Amylin receptors sit in brain regions involved in appetite control, and amylin also slows gastric emptying. The bet is that two complementary signals will do more than either one.
Two complementary signals
- 1
Cagrilintide
An amylin analogue. Amylin receptors sit in brain regions involved in appetite and amylin slows gastric emptying.
- 2
Semaglutide
A GLP-1 receptor agonist that also promotes satiety, through a different receptor.
- 3
CagriSema
The two together in one fixed combination, tested against each alone and placebo.
REDEFINE 1
REDEFINE 1 was a 68-week phase 3a trial published in the New England Journal of Medicine in 2025. It enrolled 3,417 adults without diabetes who had obesity, or overweight with a related complication. The combination was compared with semaglutide alone, cagrilintide alone and placebo, and everyone also got lifestyle intervention.
Estimated mean weight change at week 68 was -20.4% on the combination and -3.0% on placebo. Gastrointestinal adverse events affected 79.6% of the combination group and 39.9% of the placebo group. The authors describe them as mainly transient and mild to moderate.
Mean body-weight change at week 68
- Placebo-3%
- Cagrilintide plus semaglutide-20.4%
Diabetes and pooled analyses
The same combination has also been tested in type 2 diabetes, for example in the REIMAGINE 1 phase 3a study. A 2024 meta-analysis pooled earlier trials of cagrilintide alone and with semaglutide. Reading a pooled analysis next to the primary trials keeps any one result in proportion.
What the trials don't settle: longer-term outcomes, head-to-head comparison with other agents, and what happens when treatment stops. And a result from one product doesn't carry over to another, so anyone handling these peptides in a lab needs batch analysis for identity and purity.
References
- Garvey WT et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). N Engl J Med 2025.
- Dutta D et al. Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide: A Systematic Review and Meta-Analysis. Indian J Endocrinol Metab 2024.
- Aroda VR et al. Once-weekly cagrilintide-semaglutide in adults with type 2 diabetes (REIMAGINE 1). Lancet Diabetes Endocrinol 2026.
Related research notes
- Retatrutide: what the published phase 2 research shows about a triple-agonist peptideA research overview of retatrutide, an investigational GIP, GLP-1 and glucagon receptor agonist, and what its published phase 2 trials reported.
- Tirzepatide: a research overview of the GIP and GLP-1 dual agonistHow tirzepatide acts on two incretin receptors, and what the SURMOUNT-1 phase 3 trial and later reviews report about it.
- AOD-9604: the growth hormone fragment studied for lipolytic activityA review of preclinical research on AOD-9604, a modified fragment of human growth hormone, including its effects in obese rodents and how it is detected.