Abstract 13814: Semaglutide Reduces Mace Consistently Across Baseline Triglyceride Levels in Patients With Type 2 Diabetes: A Post Hoc Analysis of the Sustain 6 and Pioneer 6 Trials

Abstract

Introduction: Elevated triglyceride (TG) levels may predict CV events, although this has not been evaluated in large contemporary trials. The effects of glucagon-like peptide-1 receptor agonists on major adverse CV events (MACE) across TG levels are not fully characterized. SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) were randomized, CV outcomes trials investigating once-weekly and oral semaglutide vs placebo, respectively, in patients with type 2 diabetes at high CV risk. We performed a post hoc analysis to assess the effect of semaglutide vs placebo on the primary endpoints, MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), and its components in these two trials pooled, across baseline TG levels. Methods: The risk of first MACE with semaglutide vs placebo was evaluated across three baseline TG groups (≤151, >151-≤205, and >205 mg/dL). The effect of semaglutide vs placebo on MACE was estimated with Cox regression by TG level categorically, and continuously when adjusting for baseline TG and high-density lipoprotein-cholesterol (HDL-C) levels. The impact of statin treatment was also assessed. Results: In total, 6,417 patients had baseline TG measurements: 3,191 (49.7%) ≤151, 1,459 (22.7%) >151-≤205, and 1,767 (27.5%) >205 mg/dL; mean (±SD) TGs were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively. Overall, semaglutide reduced TGs vs placebo by 5% in SUSTAIN 6 and 6% in PIONEER 6 (p<0.01). The incidence of MACE with placebo increased across increasing TG levels (Figure) . Semaglutide generally reduced the risk of MACE and its components vs placebo across TG groups. Results were consistent when evaluating TGs as a continuous variable (adjusting for baseline TG and HDL-C levels), and regardless of statin treatment. Conclusions: In this post hoc analysis of SUSTAIN 6 and PIONEER 6, over half of patients had elevated TG levels (>151 mg/dL). Semaglutide consistently reduced the risk of MACE vs placebo across baseline TG levels.