Orforglipron in obesity and overweight in adults: durability of effect
In the population defined for obesity and overweight in adults, is the effect of Orforglipron maintained across the full duration of the contributing trials?
Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.
§1Abstract
§1.1Review question
In the population defined for obesity and overweight in adults, is the effect of Orforglipron maintained across the full duration of the contributing trials?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| 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 administered as oral once daily, without regard to food or water restriction. |
| Comparator | The comparator used in each contributing trial, reported per trial rather than pooled across comparator types. |
| Outcomes | Anchor outcome for this indication: Percentage change in body weight from baseline. Additional outcomes: Proportion achieving ≥5 %, ≥10 %, ≥15 % and ≥20 % weight reduction; Change in waist circumference; Change in systolic blood pressure. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 4 May 2024 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1,2]
§1.4Conclusion
Moderate certainty evidence bears on whether the effect of Orforglipron in obesity and overweight in adults is maintained across the randomised period. The contributing trials range in duration and the Institute reports the trajectory per trial rather than pooling across durations, because a mean at 36 weeks and a mean at 104 weeks are not estimates of the same quantity.
The conclusion rests on 3 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
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.