Orforglipron — 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 Orforglipron 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 | 44.0 | 9.0 | +35.0 | Phase 2 obesity (45 mg) |
| Vomiting | 25.0 | 2.0 | +23.0 | Phase 2 obesity |
| Constipation | 21.0 | 9.0 | +12.0 | Phase 2 obesity |
| Diarrhoea | 24.0 | 12.0 | +12.0 | Phase 2 obesity |
| Discontinuation for adverse events | 10.0 | 2.0 | +8.0 | Phase 2 obesity |
| Hepatic enzyme elevation | — | — | — | Monitored; no consistent signal reported in phase 2 |
| 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 — investigational
§4.3Warnings and precautions
- Gastrointestinal adverse-event incidence at the higher doses studied exceeded that of approved injectable agents
- As a small molecule with hepatic metabolism, drug-interaction potential differs materially from the peptide class and is not yet fully characterised
§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.
- Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, Ma X, Mather KJ, Haupt A, Robins D, Pratt E, Kazda C, Konig M. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. New England Journal of Medicine 2023;389(10):877–888. doi:10.1056/NEJMoa2302392 · PMID 37342922
- Frías JP, Hsia S, Eyde S, Liu R, Ma X, Konig M, Kazda C, Mather KJ, Haupt A, Pratt E, Robins D. Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. The Lancet 2023;402(10400):472–483. doi:10.1016/S0140-6736(23)01302-8 · PMID 37369232
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.