(2.04) Paradox in T2DM Management: Relative ineffectiveness of Oral Semaglutide in Overweight Patients - A Real-World Study

Oral semaglutide, a novel oral GLP-1 receptor agonist, is approved for treating type 2 diabetes mellitus (T2DM) with an added advantage of weight loss. This study evaluates its real-world efficacy in T2DM patients, particularly those who are overweight or obese.

Methods: We conducted a longitudinal observational study, in T2DM patients (n=171) with a BMI >25 kg/m2, who were on either 3mg, 7 mg or 14 mg dose of oral semaglutide, that was sequentially increased over three months. The patients were enrolled from February 2022 till October 2023. Semaglutide was used as a third or fourth-line agent for glycemic control and weight loss. The regimen was supplemented with dietary, exercise, and diabetes education consultations. Patient data was analyzed using GraphPad 10.1.2.3.

Results: 34% patients were on sulphonylureas, 57.35% on SGLT-2 inhibitors, 11.3% on insulin, and 42.65% on other anti hyperglycemic agents. The median clinic visit duration was 1 year. The mean patient age was 51 years (±11; 95% CI: 48 to 54). Initial mean weight of 98.7 kg (±17.7; 95% CI: 94 to 103) decreased marginally to 97.9 kg (±16.7; 95% CI: 93.4 to 102.4; p=0.8, not significant). Similarly, mean BMI reduced slightly from 36.2 kg/m^2 (±5.6; 95% CI: 34.7 to 37.7) to 35.9 kg/m2 (±4.9; 95% CI: 34.6 to 37.2; p=0.7, not significant). A modest reduction in HbA1c levels was noted from an average of 8.3% (±1.9; 95% CI: 7.7 to 8.8) to 7.7% (±1.3; 95% CI: 7.3 to 8.1; p=0.07, not significant) over 1 year of use.

Discussion/Conclusion: The study highlights a paradox in T2DM management with oral semaglutide in overweight or obese patients. Despite heightened expectations of weight and glycemic level reduction, modest improvements in HbA1c and non-significant weight/BMI changes were observed over 1 year of use of oral semaglutide possibly because of the lack of adherence to lifestyle modifications over a protracted period in the real world setting or concomitant use of sulphonylureas or insulin. These findings emphasize the need for more effective strategies to promote, adhere and sustain lifestyle changes alongside rationalised pharmacological treatments for optimal outcomes.