Comparison
Semaglutide vs Retatrutide
First-generation GLP-1 versus the triple-agonist candidate posting the largest trial weight loss to date.
Semaglutide
EstablishedBrand names: Ozempic, Wegovy, Rybelsus
Long-acting GLP-1 receptor agonist approved for type 2 diabetes and chronic weight management, with established cardiovascular benefit.
Full Semaglutide profileRetatrutide
ClinicalInvestigational triple agonist (GLP-1, GIP, glucagon) producing the largest weight loss seen in Phase II trials to date.
Full Retatrutide profile| Attribute | Semaglutide | Retatrutide |
|---|---|---|
| Category | Incretin / GLP-1 Compounds | Incretin / GLP-1 Compounds |
| Evidence tier | Established | Clinical |
| FDA status | FDA-approved (T2D and chronic weight management). Removed from FDA shortage list in early 2025, limiting compounded versions. | Investigational. Not approved. Compounding is not legally available. |
| Mechanism | Semaglutide is a GLP-1 analog that slows gastric emptying, increases satiety, enhances glucose-dependent insulin secretion, and suppresses glucagon. Its 94% homology with native GLP-1 and albumin binding extend half-life to approximately 7 days, enabling weekly dosing. | Retatrutide activates GLP-1, GIP, and glucagon receptors. The glucagon agonism is hypothesized to increase energy expenditure through hepatic and adipose effects, while the GLP-1/GIP arms drive appetite suppression. |
| Key benefits |
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| Dosage range | 0.25 – 2.4 mg weekly | 1 – 12 mg weekly (trial protocol) |
| Frequency | Weekly | Weekly |
| Route | SubQ | SubQ |
| Common side effects | Nausea (most common, dose-dependent), Constipation or diarrhea, Delayed gastric emptying, Fatigue during titration | Nausea, GI effects similar to other incretins, Transient heart rate increase, Limited long-term safety data |
Educational reference only, not medical advice. Data reflects each compound’s profile page; see individual profiles for references and full safety information.
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