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)

Abstract

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.