Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6.

INTRODUCTION: The high risk of cardiovascular events in people with type 2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type 2 diabetes at high cardiovascular risk were investigated in the SUSTAIN 6 and PIONEER 6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent. METHODS: This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70 years) pooled from SUSTAIN 6 and PIONEER 6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobin A (HbA) and body weight, and adverse events were analyzed. RESULTS: Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; p > 0.05). The treatment difference in HbA reduction was greater in those aged ≤ 60 years than in older subgroups (p = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across age subgroups (p = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups. CONCLUSION: Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA targets based solely on age may not always be required for people with type 2 diabetes. TRIAL REGISTRATION: SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) are registered at ClinicalTrials.gov.