Evaluation of the Efficacy of Semaglutide Dose Escalation in Reducing HbA1c Levels and Insulin Dose in Type 2 Diabetes Patients: Real-World Semaglutide Data from Türkiye, SEMA-TR Study

Background: Several studies have demonstrated that adding semaglutide to the treatment of patients with type 2 diabetes mellitus (T2DM) reduces insulin requirements and glycated hemoglobin (HbA1c) levels. This study aimed to investigate real-world evidence for the effects of semaglutide dose escalation on HbA1c, body weight, dyslipidemia, and insulin dose reduction in patients with T2DM in the Cukurova region of Türkiye. Methods: This retrospective cohort study enrolled 500 patients (255 male, 245 female; mean age 56.1 ± 10.8 years) who initiated semaglutide therapy for T2DM between 2024 and 2025. Patients were grouped according to their maximum semaglutide dose: 0.25 mg (Group I), 0.50 mg (Group II), and 1.00 mg (Group III). The primary endpoint was the change in HbA1c from baseline to end of study (30 weeks) across semaglutide dose escalation groups. Secondary endpoints included changes in body weight, frequency of insulin dose reduction, and effects on lipid parameters. Results: A total of 117 patients (23.4%) discontinued semaglutide therapy, while 383 patients (76.6%) completed the study. The primary endpoint revealed a mean HbA1c reduction of −1.03 ± 0.35% from baseline to end of study (95% CI 0.99–1.07; t = 58.644; p < 0.001). Reductions in HbA1c increased progressively from Group I to Group III (HbA1c: −0.72 ± 0.28, −1.02 ± 0.26, −1.27 ± 0.34%). Insulin dose reduction frequency increased significantly from Group I to Group III (40%, 41%, and 51%, respectively; p = 0.010), with a statistically significant difference only between Group I and Group III. At the end of follow-up, rates of hypoglycemic episodes and gastrointestinal (GI) adverse events were similar across groups. Conclusions: In a real-world population from the Cukurova region of Türkiye, semaglutide dose escalation in T2DM patients achieved clinically meaningful glycemic control, body weight reduction, LDL-cholesterol lowering, and a significant increase in insulin dose reduction frequency, without a significant increase in GI adverse events.