Cagrilintide and retatrutide are two of the most discussed investigational weight-management compounds, and neither is FDA-approved. Retatrutide is a triple agonist of the GLP-1, GIP and glucagon receptors. Cagrilintide is a long-acting analog of amylin, a hormone that works through a separate pathway, and it is often studied paired with semaglutide as CagriSema.
At a glance
| Cagrilintide | Retatrutide | |
|---|---|---|
| What it is | Investigational long-acting amylin analog studied for weight management, alone and with semaglutide (CagriSema) | Investigational triple GLP-1/GIP/glucagon receptor agonist studied in clinical trials for weight loss |
| How it's thought to work | Mimics amylin, a pancreatic hormone that slows gastric emptying and promotes satiety through pathways separate from GLP-1 | Activates GLP-1, GIP, and glucagon receptors together, studied for appetite suppression, insulin signaling, and energy expenditure |
| Regulatory status | Investigational; not FDA-approved | Not FDA-approved; investigational, sold outside trials only by unregulated research-chemical suppliers |
| Strength of evidence | Phase 2 human trials, alone and as CagriSema, followed by the phase 3 REDEFINE program of the combination | Human trials: a Phase 2 study (Jastreboff et al., NEJM 2023); not yet approved |
| Reported side effects | Nausea, vomiting, decreased appetite, injection site reactions | Nausea (most common), diarrhea, vomiting, constipation, decreased appetite; generally mild to moderate |
| Common vial sizes | 5mg, 10mg | 5mg, 10mg |
| Mixing math example | 5 mg + 1 mL BAC water = 5,000 mcg/mL, 50 mcg per unit | 5 mg + 1 mL BAC water = 5,000 mcg/mL, 50 mcg per unit |
Key differences
Retatrutide activates GLP-1, GIP and glucagon receptors together and is studied for appetite suppression, insulin signaling and energy expenditure. Cagrilintide mimics amylin, which slows gastric emptying and promotes fullness through receptors separate from the GLP-1 receptor.
Both are investigational. Retatrutide's published evidence includes a Phase 2 trial (Jastreboff et al., New England Journal of Medicine, 2023). Cagrilintide has Phase 2 trials alone and as CagriSema, with the phase 3 REDEFINE program studying the combination.
Both have gastrointestinal side-effect profiles. Retatrutide's most commonly reported side effect is nausea, along with diarrhea, vomiting, constipation and decreased appetite. Cagrilintide's include nausea, vomiting, decreased appetite and injection site reactions.
What the research covers
Retatrutide's Phase 2 trial and a substudy in people with fatty liver disease are its main published human data. Cagrilintide's human data comes from a Phase 2 trial of cagrilintide on its own (Lau et al., 2021) and a Phase 2 trial comparing CagriSema with each component (Frias et al., 2023). Outside clinical trials, both are sold only by unregulated research-chemical suppliers.
Sources
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, phase 2 trial. Lau DCW et al. The Lancet, 2021. Human trial
- Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias JP et al. The Lancet, 2023. Human trial
- Amylin: Pharmacology, Physiology, and Clinical Potential. Hay DL et al. Pharmacological Reviews, 2015. Review
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff AM et al. N Engl J Med, 2023. Human trial
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Sanyal AJ et al. Nature Medicine, 2024. Human trial
- Retatrutide: a triple incretin receptor agonist for obesity management. Ray A et al. Expert Opinion on Investigational Drugs, 2023. Review
Frequently asked questions
What is the difference between cagrilintide and retatrutide?
Retatrutide is a triple GLP-1, GIP and glucagon receptor agonist. Cagrilintide is an amylin analog that acts through a separate appetite pathway. Both are investigational.
Is cagrilintide or retatrutide FDA-approved?
Neither is FDA-approved. Both are investigational compounds studied in clinical trials.
Do cagrilintide and retatrutide work on the same receptors?
No. Retatrutide acts on GLP-1, GIP and glucagon receptors, while cagrilintide mimics amylin, which acts through different receptors.
Is cagrilintide the same as CagriSema?
No. CagriSema is a combination of cagrilintide with semaglutide. Cagrilintide on its own has also been studied in a Phase 2 trial.
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