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

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.

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.

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.

In this real-world study, semaglutide users who achieved glycemic and weight goals exhibited marked improvements in cardiometabolic and renal outcomes over 2 years.