Orforglipron in obesity and overweight in adults — evidence extract
The Institute's graded assessment of Orforglipron for obesity and overweight in adults, with the contributing trials and the domain-by-domain certainty reasoning.
§1Evidence extract: Obesity and overweight in adults
§1.1Question and anchor outcome
- Population
- Excess adiposity sufficient to impair health, operationalised in the pivotal incretin programmes as a body-mass index of 30 kg/m² or above, or 27 kg/m² or above with at least one weight-related comorbidity.
- Intervention
- Orforglipron, oral once daily, without regard to food or water restriction
- Comparator
- As used in each contributing trial; reported per trial rather than pooled across comparator types
- Anchor outcome
- Percentage change in body weight from baseline
Additional outcomes the Institute extracts for this indication: Proportion achieving ≥5 %, ≥10 %, ≥15 % and ≥20 % weight reduction; Change in waist circumference; Change in systolic blood pressure; Change in high-sensitivity C-reactive protein.
§1.2Contributing trials
Table 1. Trials contributing to the assessment of Orforglipron in obesity and overweight in adults.
| Trial | Phase | Design | Randomised | Duration | Year |
|---|---|---|---|---|---|
| ATTAIN-1 | 3 | Randomised, double-blind, placebo-controlled | — | 72 weeks | 2025 |
| ATTAIN-2 | 3 | Randomised, double-blind, placebo-controlled | — | 72 weeks | 2025 |
| ORFO-PH2-OBESITY | 2 | Randomised, double-blind, placebo-controlled | 272 | 36 weeks | 2023 |
§1.3Certainty assessment
Table 2. Reasoning recorded against each certainty domain.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | Serious | Differential attrition exceeded the pre-specified threshold in one arm. |
| Inconsistency | No concern | No serious concern identified in this domain. |
| Indirectness | No concern | No serious concern identified in this domain. |
| Imprecision | No concern | No serious concern identified in this domain. |
| Publication bias | No concern | No serious concern identified in this domain. |
| Overall rating: Moderate certainty. The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate. | ||
§1.4What this extract does not establish
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
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.