Semaglutide Versus Empagliflozin in Uncontrolled Type 2 Diabetes: A Cohort Study With 18 Months of Follow-Up (SEMPA18).

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic disease that substantially increases morbidity and mortality through its cardiovascular and renal complications. Beyond mere glycemic control, current guidelines from the European Society of Cardiology (ESC) and Kidney Disease: Improving Global Outcomes (KDIGO) recommend interventions that confer additional cardiovascular and renal benefits. OBJECTIVE: This study aims to assess and compare the efficacy of semaglutide versus empagliflozin in improving glycemic control, weight, blood pressure, and renal function in patients with uncontrolled T2DM after 18 months of follow-up. METHODS: This retrospective cohort study included 41 patients with uncontrolled T2DM (glycated hemoglobin (HbA1c) > 7%) who received either empagliflozin (n=20) or semaglutide (n=21) as monotherapy. Clinical and laboratory parameters (HbA1c, fasting plasma glucose, body weight, systolic and diastolic blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), and urine microalbumin) were measured at baseline and 18 months (SEMPA18). Changes were compared between the two groups using appropriate statistical methods. RESULTS: Of the 41 participants (58.5% male), 20 were treated with empagliflozin and 21 with semaglutide. After 18 months, median HbA1c decreased from 7.60% to 6.85% in the empagliflozin group (100% improved) and from 7.90% to 7.00% in the semaglutide group (95.2% improved). A reduction in body weight of 5% or more was achieved by 2 of 20 (10.0%) empagliflozin-treated patients versus 6 of 21 (28.6%) among those on semaglutide (p=0.48). Albuminuria improved in 18 of 20 (90.0%) empagliflozin users (median final: 12.0 mg/dL) compared to 14 of 21 (66.7%) semaglutide users (median final: 20.0 mg/dL), although the difference was not statistically significant (p=0.07). Both groups showed gains in eGFR (final median: 80.50 vs. 71.00 mL/min/1.73 m²; p=0.048), and serum creatinine decreased in the majority of patients (75.0% vs. 71.4%). A subgroup analysis revealed that heart failure status (LVEF < 50% or documented diagnosis) was associated with less improvement in renal markers, particularly serum creatinine, regardless of the treatment group. CONCLUSIONS: In this real-world, 18-month cohort, empagliflozin produced more pronounced improvements in albuminuria and a slightly greater absolute reduction in HbA1c, whereas semaglutide showed a trend toward greater weight loss, though not statistically significant. These findings emphasize individualized therapy choices in T2DM based on cardiorenal risk profiles and underscore the potential value of early empagliflozin initiation, especially in patients at higher risk of renal deterioration.