BACKGROUND AND AIMS: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly treatment of type 2 diabetes (T2D). In the SUSTAIN 6 cardiovascular (CV) trial, subcutaneous semaglutide (0.5 mg and 1.0 mg) added to standard of care significantly reduced major adverse CV events (MACE: non-fatal myocardial infarction, non-fatal stroke or CV death) vs placebo over 2 years in subjects with T2D at high CV risk. This post hoc analysis assessed whether this CV risk reduction was consistent in male and female subjects.
MATERIALS AND METHODS: Endpoints analysed were MACE, the individual components of the MACE endpoint, first hospitalisation due to unstable angina, first hospitalisation due to heart failure, and first revascularisation. In total, 2,002 males and 1,295 females were randomised.
RESULTS: MACE consistently occurred in fewer subjects with semaglutide vs placebo in both sexes, consistent with the overall study population (p=0.45 for interaction): HR 0.68 (95% CI 0.50;0.92) in males, 0.84 (95% CI 0.54;1.31) in females and 0.74 (95% CI 0.58;0.95) in the total study population. Overall, this pattern was reflected across the individual MACE components, showing lower rates with semaglutide vs placebo regardless of sex, with the exception of CV mortality in female subjects (Table). In the overall trial population, there was no significant difference between semaglutide vs placebo for first hospitalisation due to unstable angina or heart failure: HR 0.82 (95% CI 0.47;1.44) and 1.11 (95% CI 0.77;1.61), respectively. These results were consistent in males (HR 0.66 [95% CI 0.33;1.34] and 1.18 [95% CI 0.75;1.86], respectively) and females (HR 1.17 [95% CI 0.45;3.03] and 0.93 [95% CI 0.49;1.76]) (p=0.35 and p=0.55 for interaction, respectively). Revascularisation was performed in significantly fewer subjects with semaglutide vs placebo (HR 0.65 [95% CI 0.50;0.86], p=0.003). These results were consistent in males (HR 0.60 [95% CI 0.43;0.85], p=0.0035) and females (HR 0.74 [95% CI 0.46;1.20], not statistically significant) (p=0.50 for interaction). Adverse events were reported by similar proportions of males and females across treatments. The most frequent AEs reported were gastrointestinal, with higher rates in females than in males. The proportions of subjects prematurely discontinuing treatment due to AEs were comparable for males and females.
CONCLUSIONS: The semaglutide-induced risk reduction in MACE and its components vs placebo seen in SUSTAIN 6 was consistent in both males and females. Numerically lower proportions of females than males reported MACE. The semaglutide treatment effect on the risk of secondary CV endpoints was also similar in both sexes.