Major adverse cardiovascular events’ reduction and their association with glucose‐lowering medications and glycemic control among patients with type 2 diabetes: A retrospective cohort study using electronic health records

Background Cardiovascular diseases are a common cause of death among patients with type 2 diabetes (T2DM). Major adverse cardiovascular event (MACE) risks can be significantly reduced under adequate glycemic control (GC). This study aims to identify factors that influence MACE risk among patients with T2DM, including Hemoglobin A1c variability score (HVS) and early use of MACE‐preventive glucose‐lowering medications (GLMs). Methods We conducted a longitudinal cohort study to retrospectively review electronic health records between 2011 and 2022. Patients with T2DM ≥18 years without previous stroke or acute myocardial infarction (AMI) were included. Cox regression was utilized to investigate MACE risk factors and compare MACE risk reduction associated with early use of MACE‐preventive GLMs. Results A total of 19 685 subjects were included, with 5431 having MACE, including 4453 strokes, 977 AMI, and 1 death. There were 11 123 subjects with good baseline GC. Subjects with good baseline GC had 0.837 (confidence interval [CI]: 0.782–0.895) times lower MACE risk than their counterpart. Subjects with a single MACE‐preventive GLM at baseline with continuous use >365 days showed a decreased MACE hazard ratio (0.681; CI: 0.635–0.731). Among all MACE‐preventive GLMs, semaglutide provided a more significant MACE‐preventive effect. Conclusions This study identified that GLM, early GC, and HVS are MACE determinants among patients with T2DM. Novel GLM, adequate GC, and reduction of HVS can benefit MACE outcomes. Highlights Good baseline glycemic control (GC) can reduce the risk of future major adverse cardiovascular events (MACEs) by 16.3%. MACE risk increases as the Hemoglobin A1c variability score (HVS) increases, and the HVS boundaries differ between good GC and poor baseline GC. Subjects with MACE‐preventive glucose‐lowering medications (GLMs) at baseline had 0.681 times lower MACE risk. Among all MACE‐preventive GLMs, semaglutide potentially had the higher MACE‐preventive effect (hazard ratio [HR]: 0.439; CI: 0.141–1.364), while pioglitazone (HR: 0.825; CI: 0.714–0.954) had the least in relative.