Semaglutide reduces major adverse CV event risk in Diabetics with raised triglycerides
A posthoc analysis on SUSTAIN 6 and PIONEER 6 trial showed semaglutide was associated with consistent reduction in major Adverse cardiovascular event regardless of baseline triglyceride levels in patients with type 2 diabetes. The analysis, which was conducted by researchers from St. Michael's Hospital in Toronto and Brigham and Women's Hospital was presented at the American Heart Association's (AHA) Scientific Sessions 2020.
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. For this purpose, the researchers conducted a posthoc analysis of SUSTAIN 6 and PIONEER 6 trial to assess the effect of semaglutide vs placebo. SUSTAIN 6 enrolled 2735 patients and randomized to either 0.5 or 1g of semaglutide once weekly or placebo therapy and PIONEER 6 enrolled 3183 patients and randomized them to daily oral semaglutide or placebo.
After analyzing the data of both the trial Subodh Verma, MD, PhD, said in his presentation "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".
Upon analysis, researchers identified 6417 patients from the trials with information related to baseline triglyceride measurements and divided them into the following 3 groups:
Triglycerides level with 151 mg/dL (n=3,191) or less, triglycerides with 151 mg/dL to 205 mg/dL (n= 1,459 ), and triglycerides more than 205 mg/dL. (n=1,767). The major outcome assessed was a change in triglyceride levels over time with semaglutide versus placebo in both trials. Additionally, they also assessed MACE events (CV death, nonfatal myocardial infarction, or nonfatal stroke), and time to first MACE by triglyceride levels at baseline from the pooling data of both trials.
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. Researchers evaluated the effect of semaglutide vs placebo on MACE with Cox regression by TG level categorically, and continuously when adjusting for baseline TG and high-density lipoprotein-cholesterol (HDL-C) levels. They also assessed the impact of statin treatment.
After analysis, the researchers found semaglutide reduced triglycerides by 5% in the SUSTAIN 6 trial and 6% in the PIONEER 6 trial when compared with placebo. They noted, semaglutide generally reduced the risk of MACE and its components across all triglyceride groups when compared with placebo. They also found that the results appeared to be consistent when evaluating triglycerides as a continuous variable and regardless of statin treatment among patients.
The authors concluded, "In this post hoc analysis of SUSTAIN 6 and PIONEER 6, over half of the patients had elevated TG levels (>151 mg/dL). Semaglutide consistently reduced the risk of MACE vs placebo across baseline TG levels".
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