Cagrilintide vs Semaglutide

Cagrilintide and semaglutide act on different satiety pathways — amylin and GLP-1 — and are combined in the investigational CagriSema co-formulation.

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Cagrilintide

A long-acting amylin analogue, studied alone and in a fixed combination with semaglutide (CagriSema).

BEST STUDIED FOR

Incretin & metabolic

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	Cagrilintide	Semaglutide
The key difference	Amylin receptor agonist	GLP-1 receptor agonist
Class	Incretin & metabolic	Incretin & metabolic
Mechanism	Amylin is a pancreatic hormone co-secreted with insulin that induces satiety and slows gastric emptying.	Semaglutide is a GLP-1 analogue with amino-acid substitutions and a C18 fatty-diacid chain that binds albumin, extending its half-life to about a week.
Status	Phase 2 monotherapy data (2021) and phase 3 combination trials with semaglutide (REDEFINE, 2025–2026). Not yet approved.	Approved medicine (type 2 diabetes and chronic weight management) in many countries, with a large phase 3 programme (STEP, SUSTAIN, SELECT). Prescription-only in South Africa.
Reported safety signals	Trials report the gastrointestinal profile expected of the incretin/amylin class; the phase 1b study characterised tolerability of the combination.	Reviews document gastrointestinal effects as the most common; pancreatitis, gallbladder events and the effect on lean mass are active topics. Trials show weight regain after stopping.
A key study	A phase 2 dose-finding trial measured cagrilintide’s dose–response on body weight, safety and tolerability. (Lancet 2021, PMID 34798060)	Reviews the safety profile of semaglutide across subcutaneous and oral formulations. (Front Endocrinol (Lausanne) 2021, PMID 34305810)

Each alone answers a single-pathway question; the combination studies whether the two pathways add up. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[Cagrilintide] 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. PMID 34798060
[Cagrilintide] Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity — N Engl J Med 2025. PMID 40544433
[Cagrilintide] Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes — N Engl J Med 2025. PMID 40544432
[Semaglutide] Safety of Semaglutide — Front Endocrinol (Lausanne) 2021. PMID 34305810
[Semaglutide] A systematic review of the effect of semaglutide on lean mass: insights from clinical trials — Expert Opin Pharmacother 2024. PMID 38629387
[Semaglutide] Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial — JAMA 2021. PMID 33755728

FREQUENTLY ASKED

What is the difference between Cagrilintide and Semaglutide?

Cagrilintide and semaglutide act on different satiety pathways — amylin and GLP-1 — and are combined in the investigational CagriSema co-formulation.

What is the regulatory status of Cagrilintide and Semaglutide?

Cagrilintide: Phase 2 monotherapy data (2021) and phase 3 combination trials with semaglutide (REDEFINE, 2025–2026). Not yet approved. Semaglutide: Approved medicine (type 2 diabetes and chronic weight management) in many countries, with a large phase 3 programme (STEP, SUSTAIN, SELECT). Prescription-only in South Africa.

What safety signals have been reported?

Cagrilintide: Trials report the gastrointestinal profile expected of the incretin/amylin class; the phase 1b study characterised tolerability of the combination. Semaglutide: Reviews document gastrointestinal effects as the most common; pancreatitis, gallbladder events and the effect on lean mass are active topics. Trials show weight regain after stopping.

Which studies is this comparison based on?

For Cagrilintide: “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” (PMID 34798060); “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity” (PMID 40544433); “Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes” (PMID 40544432). For Semaglutide: “Safety of Semaglutide” (PMID 34305810); “A systematic review of the effect of semaglutide on lean mass: insights from clinical trials” (PMID 38629387); “Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial” (PMID 33755728).