Tirzepatide compared with semaglutide in type 2 diabetes
In adults with type 2 diabetes, does tirzepatide achieve greater glycaemic and weight effect than semaglutide?
§1Abstract
§1.1Review question
In adults with type 2 diabetes, does tirzepatide achieve greater glycaemic and weight effect than semaglutide?
§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 | Adults with type 2 diabetes inadequately controlled on metformin. |
| Intervention | Tirzepatide 5, 10 or 15 mg once weekly. |
| Comparator | Semaglutide 1 mg once weekly. |
| Outcomes | Change in glycated haemoglobin at week 40; change in body weight; gastrointestinal adverse events; hypoglycaemia. |
§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 5 December 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]
§1.4Conclusion
High certainty evidence from one adequately powered double-blind head-to-head trial indicates greater glycaemic and weight effect with tirzepatide at all three doses. The Institute records the material qualification that the comparator dose was 1 mg, which is not the highest approved semaglutide dose for type 2 diabetes, and that the comparison therefore establishes superiority over that dose rather than over the compound at its maximum.
The conclusion rests on 14 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Tirzepatide compared with semaglutide in type 2 diabetes received 7 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
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.
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. New England Journal of Medicine 2021;385(6):503–515. doi:10.1056/NEJMoa2107519 · PMID 34170647
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.