Tirzepatide in obesity and overweight in adults — evidence extract
The Institute's graded assessment of Tirzepatide 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
- Tirzepatide, subcutaneous once weekly
- 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 Tirzepatide in obesity and overweight in adults.
| Trial | Phase | Design | Randomised | Duration | Year |
|---|---|---|---|---|---|
| SURMOUNT-1 | 3 | Randomised, double-blind, placebo-controlled | 2,539 | 72 weeks | 2022 |
| SURMOUNT-2 | 3 | Randomised, double-blind, placebo-controlled | 938 | 72 weeks | 2023 |
| SURMOUNT-3 | 3 | Randomised, double-blind, placebo-controlled | 806 | 72 weeks after a 12-week lead-in | 2023 |
| SURMOUNT-4 | 3 | Randomised withdrawal | 670 | 52 weeks after a 36-week open-label lead-in | 2024 |
| SURMOUNT-5 | 3 | Randomised, open-label, active-controlled | 751 | 72 weeks | 2025 |
§1.3Certainty assessment
Table 2. Reasoning recorded against each certainty domain.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | No concern | No serious concern identified in this domain. |
| 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: High certainty. The Institute is confident that the true effect lies close to the estimate. Further research is very unlikely to change 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.
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine 2022;387(3):205–216. doi:10.1056/NEJMoa2206038 · PMID 35658024
- Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2023;402(10402):613–626. doi:10.1016/S0140-6736(23)01200-X · PMID 37385275
- Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine 2023;29(11):2909–2918. doi:10.1038/s41591-023-02597-w · PMID 37840095
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.