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

Background: Semaglutide is a GLP1-RA for the treatment of type 2 diabetes. 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, subjects with T2D and established cardiovascular disease or high CV risk were randomised to subcutaneous semaglutide 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 vs. those receiving placebo over 2 years. 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. 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. 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. 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. Conclusion: Consistent CV risk reduction with semaglutide vs. comparators was observed across T2D populations at different levels of CV risk at baseline.