Orforglipron — clinical evidence
Assessed outcomes with certainty ratings, contributing trials and the reasoning for each rating.
§3Clinical evidence
§3.1Obesity and overweight in adults
Anchor outcome. Percentage change in body weight from baseline.
Effect as recorded. −14.7 % body weight at 36 weeks with 45 mg in the phase 2 trial versus −2.3 % with placebo; estimated difference −12.4 percentage points (95 % CI −14.8 to −10.0).[1,2]
Certainty. Moderate certainty Phase 2 at 36 weeks with weight still declining at the final timepoint, so the plateau effect is unknown. Downgraded for indirectness of duration.
Contributing trials. ATTAIN-1 · ATTAIN-2 · ORFO-PH2-OBESITY. Full structured abstracts are published for each.
Full evidence extract for obesity and overweight in adults · Indication assessment
§3.2Type 2 diabetes mellitus
Anchor outcome. Change in HbA1c (%, mmol/mol).
Effect as recorded. −2.1 % HbA1c at 26 weeks with 45 mg versus −0.4 % with placebo; estimated difference −1.7 % (95 % CI −2.1 to −1.3).[2,3]
Certainty. Moderate certainty Phase 2 dose-response with a clear gradient.
Contributing trials. ACHIEVE-1 · ACHIEVE-2 · ORFO-PH2-T2D. Full structured abstracts are published for each.
Full evidence extract for type 2 diabetes mellitus · Indication assessment
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
- Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism 2018;27(4):740–756. doi:10.1016/j.cmet.2018.03.001 · PMID 29617641
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