Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk
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Aim: To investigate the effects of semaglutide versus comparators on major adverse cardiovascular events (MACE: cardiovascular [CV] death, nonfatal myocardial infarction [MI] and nonfatal stroke) and hospitalization for heart failure (HF) in the SUSTAIN (subcutaneous semaglutide) and PIONEER (oral semaglutide) trials across subgroups of varying CV risk. Methods: Post hoc analyses of individual patient‐level data combined from SUSTAIN 6 and PIONEER 6 were performed to assess MACE and HF. MACE were analysed in subjects with and without: established CV disease and/or chronic kidney disease; prior MI or stroke; and prior HF. MACE in the SUSTAIN and PIONEER glycaemic efficacy trials were also assessed. Results: In SUSTAIN 6 and PIONEER 6 combined, the hazard ratio (HR) for effect of semaglutide versus placebo on overall MACE was 0.76 (95% CI 0.62, 0.92), which was mainly driven by the effect on nonfatal stroke (HR 0.65 [95% CI 0.43, 0.97]). The HR for hospitalization for HF was 1.03 (95% CI 0.75, 1.40). The HRs for MACE were <1.0 in all subgroups, except for those with prior HF (HR 1.06 [95% CI 0.72, 1.57]); P ‐values for interaction of subgroup on treatment effect were >0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33). Conclusions: In SUSTAIN and PIONEER combined, glucagon‐like peptide‐1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF.
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The semaglutide CVOTs did not show an increased incidence of hospitalization for heart failure compared to placebo.
“the semaglutide CVOTs did not show an increased incidence of hospitalization for HF compared to placebo”
From Safety of Semaglutide (2021) · cites this paper as [101]
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- Authors
- Husain, M., Bain, S. C., Jeppesen, O. K., Lingvay, I., Sørrig, R., Treppendahl, M. B., & Vilsbøll, T.
- Affiliations
- Ted Rogers Centre for Heart Research (CA)
- Swansea University (GB)
- Novo Nordisk (Denmark) (DK)
- The University of Texas Southwestern Medical Center (US)
- University of Copenhagen (DK)
- Corresponding author
- Husain, Mansoor
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2020-02-05
- Volume
- 22
- Issue
- 3
- Pages
- 442-451
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC7064975
- OpenAlex
- W2998275298
- Cited by
- 209
- References
- 42
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 40 · 2023: 41 · 2022: 35 · 2021: 21 · 2020: 22
- FWCI
- 22.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Funders
- Steno Diabetes Center Copenhagen (SDCC 3.F CMP)
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- semaglutide, type 2 diabetes, major adverse cardiovascular events, heart failure hospitalization, GLP-1 receptor agonists, old myocardial infarction, stroke history, chronic kidney disease, SUSTAIN 6, Pioneer 6, subgroup analysis
- MeSH terms
- Heart Disease Risk Factors, Semaglutide, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Humans, Hypoglycemic Agents, Risk Factors
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