Analysis Indicates Semaglutide Reduces MACE Regardless of Triglyceride Levels

This article was originally published on EndocrinologyNetwork.com.

Subodh Verma, MD

An analysis of data from the SUSTAIN 6 and PIONEER 6 trials indicates use of semaglutide was associated with consistent reductions in major adverse cardiovascular events regardless of baseline triglyceride levels in patients with type 2 diabetes.

The analysis, which was conducted by investigators from St. Michael’s Hospital in Toronto and Brigham and Women’s Hospital, aggregated data from the SUSTAIN 6 and PIONEER 6 trials and concluded semaglutide reduced the risk of major adverse cardiovascular events across multiple levels of baseline triglycerides.

“We found that the incidence rate for MACE in the placebo arm increased across increasing triglyceride levels as evaluated categorically in this analyses. Semaglutide generally reduced the risk of MACE and its components versus placebo across all triglyceride groups,” said Subodh Verma, MD, PhD, a cardiac surgeon-scientist at St. Michael’s Hospital, in his AHA 2020 presentation. “Results were consistent when evaluating triglycerides categorically or as a continuous variable.”

Presented at the American Heart Association’s (AHA) Scientific Sessions 2020, the current study was designed as a posthoc analysis of the trials to assess effects of semaglutide on MACE and its components across triglyceride levels. Briefly, SUSTAIN 6 enrolled 2735 patients and randomized to either 0.5 or 1g semaglutide once weekly or placebo therapy and PIONEER 6 enrolled 3183 and randomized them to daily oral semaglutide or placebo.

The main outcome of interest for the analysis was change in triglyceride levels over time with semaglutide versus placebo in both trials. Additionally, Investigators hoped to determine the risk of first MACE and its components by baseline triglyceride levels and time to first MACE by triglyceride levels at baseline for semaglutide and placebo when pooling data from both trials.

Upon analysis, investigators identified 6417 patients from the trials with information related to baseline triglyceride measurements, These groups were defined as triglycerides 151 mg/dL or less, 151 mg/dL to 205 mg/dL, and more than 205 mg/dL. Results indicated the mean triglycerides for each of the 3 groups were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively.

Investigators estimated the effect of semaglutide versus placebo on primary endpoints using Cox regression by triglyceride level categorically and continuously when adjusted for baseline triglycerides and HDL cholesterol. Investigators also noted the analysis was designed to assess impact of statin treatment in these patients as well.

After analysis, investigators determined semaglutide reduced triglycerides versus placebo by 5% in the SUSTAIN 6 trial and 6% in the PIONEER 6 trial (P <.01). Further analysis indicated the incidence of MACE with placebo increased across the increasing triglyceride groups. In comparison, semaglutide generally reduced the risk of MACE and its components across all triglyceride groups versus placebo. Additionally, results appeared to be consistent when evaluating triglycerides as a continuous variable and regardless of statin treatment among patients.

“This posthoc analysis of SUSTAIN 6 and PIONEER 6 trials pooled demonstrated that semaglutide reduced triglyceride levels versus placebo in both trials, in which over half of the patients had elevated levels at baseline,” Verma added.

This study, “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,” was presented at AHA 2020.