Oral and Subcutaneous Semaglutide Show Comparable Efficacy in Lowering HbA1c and BMI in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose, leading to significant microvascular and macrovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a cornerstone of T2DM management, offering potent glucose-lowering effects, weight reduction, and cardiovascular benefits. Semaglutide is unique as the only GLP-1RA available in both subcutaneous (injectable) and oral formulations, providing flexibility for patients. However, real-world comparative data on the effectiveness of these two administration routes on metabolic and cardiovascular risk factors has been limited, leaving a gap in understanding their relative utility.

This retrospective real-world study included 434 adult patients with Type 2 Diabetes Mellitus from the ASUGI Diabetes Center, comparing those treated with oral semaglutide (n = 232) versus subcutaneous semaglutide (n = 202). Patients had a median age of 70 years and diabetes duration of 13 years. Data were analyzed for an 18-month follow-up period for 130 oral and 145 subcutaneous patients. To address baseline differences, particularly in BMI, propensity score matching was performed, yielding 55 matched pairs. Primary endpoints included changes in HbA1c and BMI, with secondary analyses on blood pressure and lipid profiles, and the impact of concomitant SGLT2 inhibitor therapy.

Both oral and subcutaneous semaglutide formulations demonstrated comparable effectiveness in improving metabolic parameters. Multivariate linear regression models indicated that both were similarly effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. After propensity score matching for 55 pairs, there were no significant differences in the median change in HbA1c or BMI between the oral and subcutaneous groups. However, a notable distinction emerged:

Oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the subcutaneous formulation. Furthermore, the study observed that concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol across both semaglutide groups. The oral formulation did exhibit a higher discontinuation rate, though specific percentages were not provided in the abstract.