Cardiometabolic and Renal Outcomes in Semaglutide Users with Type 2 Diabetes Achieving Glycemic and Weight Goals: An Observational Cohort Study.

INTRODUCTION: Within the cardiovascular-kidney-metabolic syndrome (CKM) framework, semaglutide has demonstrated benefits beyond glycemic control and weight loss in clinical trials. However, most real-world studies in type 2 diabetes (T2D) have limited assessment of broader cardiometabolic and renal outcomes. We evaluated CKM-relevant outcomes among individuals with T2D who achieved substantial hemoglobin A1c (HbA1c) and weight improvements after initiating semaglutide in real-world settings. METHODS: This observational pre-post study used Optum's de-identified Market Clarity Data from January 1, 2007, to June 30, 2024. The primary cohort comprised individuals with T2D who achieved glycemic control (HbA1c < 7%) and weight loss (≥ 5%) goals after semaglutide initiation. We compared baseline (1 year before initiation) with 1st-year and 2nd-year follow-up for cardiometabolic endpoints (3-point and 5-point major adverse cardiovascular events [MACE]), cardiometabolic risk factors, and renal outcomes. Sensitivity analysis was performed in an exploratory cohort of patients in the top tertile of Hb1Ac reduction and weight loss. RESULTS: We identified 413 patients in the primary cohort (mean age 59.6 years and balanced sex distribution). Significant reductions were observed in low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), total cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure and high-density lipoprotein cholesterol (HDL-C) increased at both 1 and 2 years after semaglutide initiation (all p < 0.001). Fewer than 1% of patients experienced a ≥ 40% decline in estimated glomerular filtration rate (eGFR) during follow-up. Mean change in urine albumin-to-creatinine ratio (UACR) were - 20.13 mg/g in the 1st year (p < 0.001) and - 54.03 mg/g in the 2nd year (p < 0.001). The event rate of 3-point MACE decreased from 26.82 per 1000 person-years (PY) during baseline to 22.31 per 1000 PY in the 2nd year. The sensitivity analysis showed consistent results. CONCLUSION: In this real-world study, semaglutide users who achieved glycemic and weight goals exhibited marked improvements in cardiometabolic and renal outcomes over 2 years.