Search

Objective: Semaglutide, a glucagon-like peptide 1 receptor agonist, reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) at high risk of cardiovascular disease (CVD) in a post hoc analysis of pooled data from Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN) 6 and Peptide Innovation for Early Diabetes Treatment (PIONEER) 6. We estimated the benefit of adding semaglutide to standard of care (SoC) on life-years free of new/recurrent CVD events in people with T2D at high risk of CVD., Research Design and Methods: The Diabetes Lifetime-perspective prediction (DIAL) competing risk-adjusted lifetime CVD risk model for people with T2D was developed previously. Baseline characteristics of the pooled cohort from SUSTAIN 6 and PIONEER 6 (POOLED cohort) (N = 6,480) were used to estimate individual life expectancy free of CVD for patients in the POOLED cohort. The hazard ratio of MACE from adding semaglutide to SoC was derived from the POOLED cohort (hazard ratio [HR] 0.76 [95% CI 0.62-0.92]) and combined with an individual's risk to estimate their CVD benefit., Results: Adding semaglutide to SoC was associated with a wide distribution in life-years free of CVD gained, with a mean increase of 1.7 (95% CI 0.5-2.9) life-years. Estimated life-years free of CVD gained with semaglutide was dependent on baseline risk (life-years free of CVD gained in individuals with established CVD vs. those with cardiovascular risk factors only: 2.0 vs. 0.2) and age at treatment initiation., Conclusions: Adding semaglutide to SoC was associated with a gain in life-years free of CVD events that was dependent on baseline CVD risk and age at treatment initiation. This study helps contextualize the results of semaglutide clinical trials., (© 2022 by the American Diabetes Association.)

In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes in both the "established CV disease" (CVD) and "CV risk factor" subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD from those used in REWIND. The present post hoc analysis assessed the effect of semaglutide on major adverse CV events (MACE) in a pooled population of SUSTAIN 6 and PIONEER 6 patients, re-categorized into CV risk subgroups using the REWIND CVD criteria. In the pooled analysis (n = 6480), a lower percentage of patients were in the established CVD subgroup, when using the REWIND CVD criteria, compared with the original trial CVD criteria (66.5% vs. 83.8%, respectively). After re-categorization, the risk of MACE was significantly lower with semaglutide versus placebo in the established CVD subgroup (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.59, 0.92) and nonsignificantly lower in the CV risk factor subgroup (HR 0.84, 95% CI 0.55, 1.28) (P-interaction = 0.60). These results suggest that the CV effects of semaglutide may extend to patients with type 2 diabetes across the CV risk continuum., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)