Abstract 122: Multifactorial risk reduction with oral semaglutide vs comparators in the treatment of type 2 diabetes

Background and Aims: Therapies that address multiple risk factors may help patients with type 2 diabetes (T2D) to improve their cardiometabolic risk profile. This exploratory analysis aimed to evaluate the efficacy of oral semaglutide in improving multiple cardiometabolic risk factors vs comparators. Materials and Methods: In the PIONEER phase 3a clinical trial programme, patients with T2D were randomised to oral semaglutide 14 mg/flex (flexible dose adjustment for PIONEER 7 only) or comparators (empagliflozin 25 mg, sitagliptin 100 mg, liraglutide 1.8 mg or placebo [pbo]). This post hoc analysis evaluated the proportion of patients who achieved specific cardiometabolic endpoints (reductions in HbA1c 3 1%, body weight 3 5%, systolic BP 3 5 mmHg or LDL cholesterol 3 0.5 mmol/L or an increase in eGFR 3 0 mL/min/1.73 m2) by the end of the PIONEER 1-8 trials, and the proportion achieving 2,3 and 4 or more of these endpoints. Data were analysed using a logistic regression model with treatment, strata (PIONEER 3-8), interaction strata (PIONEER 5 and 8) and region as categorical fixed effects and baseline value as covariate for the on–treatment without rescue medication data for all randomised patients. Results: Across trials, greater proportions of patients achieved each endpoint with oral semaglutide vs comparators. Reductions in HbA1c 3 1% occurred in 47.3-77.1% with oral semaglutide vs 32.8-51.4% with active comparators or 8.5-23.7% with pbo. Reductions in body weight 3 5% occurred in 30.8-49.8% with oral semaglutide vs 12.7-41.0% with active comparators or 5.4-16.3% with pbo. Reductions in systolic BP 3 5 mmHg occurred in 47.9-62.5% with oral semaglutide vs 48.8-59.7% with active comparators or 40.1 – 57.9% withpbo. Reductions in LDL cholesterol 3 0.5 mmol/L occurred in 20.2-27.4% with oral semaglutide vs 13.7-21.1 with active comparators or 12.7-21.7% with pbo. Increases in eGFR 3 0 mL/min/1.73 m2 occurred in 45.1-54.6% with oral semaglutide vs 37.0-50.0% with active comparators or 32.4-44.5% with pbo. Significantly greater proportions of patients achieved improvements in 2,3 or 4 or more endpoints with oral semaglutide vs comparators across all trials, except for achievement of 2 endpoints with oral semaglutide 14 mg vs liraglutide 1.8 mg in PIONEER 4. Conclusion: Multifactorial risk factor management is fundamental to long-term risk reduction in patients with T2D. Oral semaglutide was more effective at improving multiple cardiometabolic risk factors vs comparators, indicating its potential to help address the full cardiometabolic profile for patients with T2D.