CagriSema vs Retatrutide
A detailed comparison to help you understand the differences and choose the right peptide for your research goals.
CagriSema
CagriSema is a fixed-ratio combination of cagrilintide (a long-acting amylin analog) and semaglutide, developed by Novo Nordisk. By combining two distinct appetite-regulating peptide hormones, CagriSema aims to achieve greater weight loss than semaglutide alone. Phase 3 data showed 22.7% body weight reduction, and an FDA response is expected in 2026.
Full details →Retatrutide
Retatrutide (LY3437943) is a first-in-class triple agonist peptide targeting GIP, GLP-1, and glucagon receptors simultaneously. Developed by Eli Lilly, it is currently in Phase 3 clinical trials and has demonstrated the highest weight loss of any obesity medication to date — up to 28.7% body weight reduction at 48 weeks. The triple-receptor mechanism represents the next evolution beyond dual agonists like tirzepatide.
Full details →Side-by-Side Comparison
| Aspect | CagriSema | Retatrutide |
|---|---|---|
| Dose Range | — | 4 mg–12 mg |
| Frequency | Less than daily | Less than daily |
| Route | subcutaneous | subcutaneous |
| Mechanism | CagriSema combines two complementary peptide mechanisms: (1) Semaglutide — GLP-1 receptor agonist providing glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and hypothalamic appetite suppression. (2) Cagrilintide — a long-acting analog of amylin, a peptide hormone co-secreted with insulin from pancreatic beta cells. Amylin activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and hypothalamus, providing additional appetite suppression via a distinct neuronal pathway from GLP-1. The combination produces additive weight loss by engaging two independent satiety signaling systems. | Retatrutide is a synthetic peptide that activates three incretin/metabolic hormone receptors: (1) GLP-1 receptor — appetite suppression, insulin secretion, delayed gastric emptying, (2) GIP receptor — enhanced insulin sensitivity, improved fat metabolism, (3) Glucagon receptor — increased energy expenditure, hepatic fat mobilization, thermogenesis. The glucagon receptor component is the key differentiator, adding an energy-expenditure mechanism absent from GLP-1 and dual GIP/GLP-1 agonists. The molecule uses a C20 fatty diacid for albumin binding, enabling once-weekly dosing. |
| Typical Dosage | Phase 3 trial doses: cagrilintide 2.4 mg + semaglutide 2.4 mg weekly (fixed combination in a single injection). Dose escalation: start at cagrilintide 0.15 mg / semaglutide 0.25 mg weekly and escalate over 16 weeks to the maintenance dose. Administered as a single injection combining both peptides. | Phase 2 trial doses: 0.5 mg, 4 mg, 8 mg, and 12 mg weekly. The 12 mg dose produced maximum weight loss (28.7%). Phase 3 trials are evaluating doses up to 12 mg. Dose escalation schedule similar to other GLP-1s (start low, increase every 4 weeks). Final approved dosing not yet established — Phase 3 trials ongoing. |
| Administration | Single subcutaneous injection once weekly, combining both peptides. Pre-filled pen device. Not yet commercially available. FDA response expected 2026. | Subcutaneous injection, once weekly. Phase 3 trials use pre-filled single-dose pens. Not yet commercially available — estimated FDA approval ~2027-2028. |
| Side Effects | Phase 3 data: nausea, vomiting, diarrhea, constipation (similar profile to semaglutide alone, but some reports suggest modestly higher GI rates). Decreased appetite. Injection site reactions. | Phase 2 data: nausea (up to 25%), diarrhea (up to 22%), vomiting (up to 15%), constipation, decreased appetite. GI side effects were dose-dependent and generally mild-to-moderate. Lower rates of nausea compared to semaglutide, potentially due to GIP component. Increased heart rate observed at higher doses. |
| Best For |
What They Have in Common
CagriSema, Retatrutide are both commonly used for:
Which Has Stronger Evidence?
| Goal | CagriSema | Retatrutide |
|---|---|---|
| Weight Loss | high | high |
| Diabetes Management | medium | medium |
Key Studies
CagriSema
- Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study.
The lancet. Diabetes & endocrinology, 2026
- Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study.
The lancet. Diabetes & endocrinology, 2026
- Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study.
Lancet (London, England), 2026
Retatrutide
- Retatrutide in type 2 diabetes mellitus and obesity: an overview.
Expert review of clinical pharmacology, 2026
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials.
Diabetes, obesity & metabolism, 2026
- Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2026
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