Semaglutide consistently reduces cardiovascular risk in patients with type 2 diabetes regardless of baseline cardiovascular risk level: post hoc analyses of the SUSTAIN trial programme

Abstract

BACKGROUND: Semaglutide is a glucagon-like peptide-1 analogue for the once-weekly treatment of type 2 diabetes (T2D). Treatment with semaglutide led to significant reductions in HbA1c and body weight vs all comparators across the SUSTAIN phase 3a clinical trial programme. In SUSTAIN 6, 3,297 subjects with T2D and established cardiovascular (CV) disease or high CV risk (subclinical evidence of CV disease) were randomised to subcutaneous semaglutide (0.5 or 1.0 mg) or placebo, added to standard of care; the median duration of follow-up was 2.1 years. Semaglutide-treated patients had a significant 26% lower risk of major adverse CV events (MACE: a primary composite outcome of non-fatal myocardial infarction [MI], non-fatal stroke or CV death) vs those receiving placebo over 2 years (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58; 0.95).

PURPOSE: To assess the consistency of the CV effect of semaglutide across subgroups at different CV risk levels in SUSTAIN 6. Additionally, to examine the risk of MACE in the SUSTAIN 1–5 phase 3a trials, which included subjects at lower CV risk (n=4,807).

METHODS: In SUSTAIN 6, two post hoc subgroup analyses were performed, each dividing the population into two CV risk levels at baseline: 1) prior MI or stroke (yes/no); 2) CV risk factors vs established CV disease (prior stroke, ischaemic heart disease [including prior MI], peripheral arterial disease, ≥50% arterial stenosis [any artery] or heart failure). A post hoc meta-analysis of MACE in the SUSTAIN 1–5 trials was also conducted.

RESULTS: In SUSTAIN 6, HRs for MACE were consistently below 1.0 across subgroups with no significant interactions (Figure). The HR for MACE in the SUSTAIN 1–5 trials was 0.85 (95% CI 0.35; 2.06), with the wide CI reflecting the low number of events.

CONCLUSIONS: Consistent CV risk reduction with semaglutide vs comparators was observed across T2D populations at different levels of CV risk at baseline.

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