Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes.

Background: No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate.

Objective: The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A_1C (HbA_1C) and weight in patients with type 2 diabetes (T2D).

Methods: This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA_1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients' primary care office.

Results: A total of 105 patients were included. Patients experienced mean decreases in HbA_1C and weight from baseline to 6 months of -1.75% (P < 0.001) and -3.64 kg (P = 0.015), respectively, in the oral semaglutide group and -1.35% (P < 0.001) and -5.26 kg (P < 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA_1C (P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight (P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide.

Conclusion: In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA_1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA_1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.