BackgroundThe SUSTAIN-6 trial showed the cardiovascular disease (CVD) benefits of semaglutide among patients with type 2 diabetes mellitus (T2DM). We estimated the US population eligibility and preventable CVD events from semaglutide.MethodsUS adults with T2DM were selected from the National Health and Nutrition Examination Survey 2011-2020 based on SUSTAIN-6 eligibility criteria. We estimated composite and secondary CVD events from SUSTAIN-6 treated and placebo published event rates multiplied by the weighted US eligible population, the difference being the number of preventable events which was then divided by 2.1 years to provide annualized estimates.ResultsAmong 4755 (projected to 33.6 million [M]) adults with T2DM, 1132 (6.9 million) fit SUSTAIN-6 criteria. Compared to SUSTAIN-6, our sample more likely had female and black patients, shorter diabetes duration, and was less likely with prior CVD. We estimated 75,681 primary outcome CVD events, 128,329 expanded composite CVD events, 72,390 combined nonfatal MI, nonfatal stroke, and all-cause deaths, 36,195 non-fatal stroke events, 85,552 revascularizations, and 75,681 cases of nephropathy could be prevented annually if eligible T2DM subjects were on semaglutide.ConclusionSemaglutide may prevent over 75,000 CVD events annually if provided to eligible T2DM US adults. Efforts to improve use of these therapies are needed.