The Impact of Oral Semaglutide on Glycemic Control and Weight Reduction: A Database Analysis of Dosing Effects in Japanese Individuals with Type 2 Diabetes

Mizuki Ishiguro^*Rimei Nishimura

• Division of Diabetes, Metabolism and Endocrinology, The Jikei University School of Medicine, Tokyo, Japan

Objective: GLP-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events in type 2 diabetes (T2D), and oral formulations improve accessibility. However, their real-world effectiveness and predictors of response remain unclear.This study assessed the proportions of individuals achieving HbA1c <7.0% and experiencing ≥3.0% weight reduction after 180 days of maintenance-dose therapy (no dose modification for ≥180 days). Methods: We retrospectively analyzed 169 participants with T2D (3 mg: n=45; 7 mg: n=92; 14 mg: n=32) treated at a single medical care center in Japan. The cohort included participants with HbA1c ≥7.0% at baseline. We evaluated semaglutide changes in HbA1c and weight, and predictors of glycemic response after 180 days of maintenance therapy using logistic regression. Results: Baseline characteristics included median age 63.0 years, body mass index (BMI) 27.2 kg/m², diabetes duration 10.0 years, and HbA1c 7.7%. Oral semaglutide was initiated as the first or second choice in 45.0% of participants. HbA1c <7.0% was achieved in 60.0%, 53.3%, and 46.9% of the 3 mg, 7 mg, and 14 mg groups, respectively. Weight reduction ≥3.0% occurred in approximately half of participants across all groups. Lower baseline HbA1c (B = -1.330, p < 0.001) and earlier semaglutide use (first/second choice; B = 1.070, p = 0.013) were significant predictors of HbA1c <7.0%. Conclusion: Approximately 50% of participants across all dosing groups achieved HbA1c<7.0% after 180 days of maintenance therapy. Weight reduction (≥3.0%) occurred frequently in parallel with HbA1c reduction. Early semaglutide use (first/second choice) and lower baseline HbA1c predicted HbA1c <7.0% on maintenance therapy.