Efficacy and safety of oral semaglutide as add-on therapy in poorly controlled type 2 diabetes on background SGLT2 inhibitors: a real-world, multi-center, retrospective, observational study (RYS2).

BACKGROUND: Treatment of type 2 diabetes mellitus (T2DM) relies on diverse glucose-lowering medications, championing sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists as viable options to address concurrent cardiovascular risk. An oral formulation of semaglutide (Rybelsus, Novo Nordisk) has been recently introduced to clinical use for managing T2DM. Accordingly, there is a paucity of practice evidence while building experience on its combination with SGLT2i. METHODS: In this observational, single-arm, retrospective study, data collected from 142 T2DM patients (66% males, 68% older than 60 years, 85% overweight/obese) treated with oral semaglutide in combination with SGLT2i were analyzed. RESULTS: After 6.8±2.6 months of treatment, both glycosylated hemoglobin (HbA1c) and fasting plasma glucose levels significantly improved: 39.6% of patients achieved HbA1c<inf>DCCT</inf> ≤7% (HbA1c<inf>IFCC</inf> ≤53.0 mmol/mol) and 18.8% experienced both a decrease of HbA1c ≥1% and a weight loss ≥5%. In addition, body weight, body mass index, waist circumference, triglycerides, and total cholesterol levels were significantly reduced. Regarding safety, 94.7% of reported adverse events were non-serious gastrointestinal symptoms and 1 patient experienced hypoglycemia. CONCLUSIONS: The herein presented real-world data suggest that oral semaglutide can be regarded as safe and effective, when used as add-on medication for uncontrolled T2DM on background SGLT2i.