Retatrutide — safety
Adverse events as reported, contraindications, warnings, and an explicit statement of what the safety evidence does not establish.
§4Safety
§4.1Adverse events reported in controlled trials
Table 4. Adverse events for Retatrutide as reported in the trial safety tables the Institute holds. Percentages are of randomised participants in the stated trial and arm.
| Event | Active, % | Comparator, % | Difference, pp | Source |
|---|---|---|---|---|
| Nausea | 35.0 | 13.0 | +22.0 | Phase 2 obesity trial (12 mg, 48 weeks) |
| Diarrhoea | 29.0 | 9.0 | +20.0 | Phase 2 obesity |
| Vomiting | 24.0 | 2.0 | +22.0 | Phase 2 obesity |
| Constipation | 20.0 | 9.0 | +11.0 | Phase 2 obesity |
| Increased heart rate | — | — | — | Dose-dependent rise of approximately 6–10 beats/min at higher doses, attenuating by week 24 |
| Discontinuation for adverse events | 16.0 | 4.0 | +12.0 | Phase 2 obesity (highest dose cohort) |
| A difference column is computed by the Institute from the two reported percentages and is not itself a published figure. Confidence intervals for adverse-event differences are not reported in the contributing trials and are not constructed here. | ||||
§4.2Contraindications
- Not established — the compound has no marketing authorisation and therefore no approved contraindication list
§4.3Warnings and precautions
- A dose-dependent increase in heart rate distinguishes this compound from the selective GLP-1 class and has not been characterised over a multi-year horizon
- Glucagon receptor agonism raises theoretical concerns about hepatic glucose output and amino-acid metabolism that long-term data have not yet addressed
- Gastrointestinal discontinuation rates at the highest doses studied were substantially above those of approved agents
§4.4What this section does not establish
Related assessments: tolerability of incretin receptor agonists · acute pancreatitis · the rodent thyroid C-cell signal.[1,2]
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. New England Journal of Medicine 2023;389(6):514–526. doi:10.1056/NEJMoa2301972 · PMID 37366315
- Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, parallel-group, phase 2 trial. The Lancet 2023;402(10401):529–544. doi:10.1016/S0140-6736(23)01053-X · PMID 37385280
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.