Semaglutide in type 2 diabetes mellitus — evidence extract
The Institute's graded assessment of Semaglutide for type 2 diabetes mellitus, with the contributing trials and the domain-by-domain certainty reasoning.
§1Evidence extract: Type 2 diabetes mellitus
§1.1Question and anchor outcome
- Population
- A disorder of glucose regulation characterised by insulin resistance with relative insulin deficiency, diagnosed by glycated haemoglobin, fasting plasma glucose or oral glucose tolerance criteria.
- Intervention
- Semaglutide, subcutaneous once weekly; oral once daily with a permeation enhancer (see separate monograph)
- Comparator
- As used in each contributing trial; reported per trial rather than pooled across comparator types
- Anchor outcome
- Change in HbA1c (%, mmol/mol)
Additional outcomes the Institute extracts for this indication: Proportion achieving HbA1c <7.0 % and ≤6.5 %; Change in fasting serum glucose; Change in body weight; Documented symptomatic hypoglycaemia.
§1.2Contributing trials
Table 1. Trials contributing to the assessment of Semaglutide in type 2 diabetes mellitus.
| Trial | Phase | Design | Randomised | Duration | Year |
|---|---|---|---|---|---|
| SUSTAIN-1 | 3 | Randomised, double-blind, placebo-controlled | 388 | 30 weeks | 2017 |
| SUSTAIN-6 | 3 | Event-driven cardiovascular outcome trial | 3,297 | 104 weeks | 2016 |
| SUSTAIN-7 | 3 | Randomised, double-blind, active-controlled | 1,201 | 40 weeks | 2018 |
| STEP-2 | 3 | Randomised, double-blind, placebo-controlled | 1,210 | 68 weeks | 2021 |
§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.
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183 · PMID 33567185
- Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet 2021;397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0 · PMID 33667417
- Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O’Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA 2021;325(14):1403–1413. doi:10.1001/jama.2021.1831 · PMID 33625476
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.