O-SEMA-FAST: A Prospective, Non-interventional Study Investigating Oral Semaglutide Use in Adults with Type 2 Diabetes Mellitus During Ramadan.

INTRODUCTION: Oral semaglutide, a glucagon-like peptide 1 receptor agonist, requires administration on an empty stomach with up to 120 mL of water, followed by no intake of food, beverages, or other oral medications for at least 30 min to ensure optimal absorption. These instructions can be challenging to adhere to during Ramadan when patients fast for extended periods. The O-SEMA-FAST study assessed the impact of fasting on adherence to oral semaglutide dosing instructions and its subsequent effects on glycaemic control and body weight. METHODS: O-SEMA-FAST was a non-interventional, prospective study conducted in 2023 in people with type 2 diabetes mellitus (T2DM) who fasted during Ramadan and were on oral semaglutide treatment in the United Arab Emirates, Saudi Arabia, and Kuwait. Patients were followed for 20 weeks. Glycated haemoglobin (HbA1c) and body weight were measured at baseline and at the end of the study (EOS); changes were analysed by mixed models for repeated measures. RESULTS: Among the 257 patients included in the final analysis, there was a significant reduction in HbA1c (- 0.2%-points, p = 0.01) and a notable decrease in body weight (- 2.6 kg, p < 0.0001) from baseline to EOS. Of the 215 patients who recorded administration details in their diaries, 68.4% (n = 147) adhered to dosing instructions for ≥ 80% of diary days. Baseline mean HbA1c was 6.7% in adherent patients and 7.0% in non-adherent patients. At EOS, the change in HbA1c was - 0.3%-points (95% confidence interval, CI - 0.4, - 0.2; p < 0.0001) for adherent patients and - 0.1%-points (95% CI - 0.4, 0.1; p = 0.3) for non-adherent patients. The change in body weight was - 3.2 kg (95% CI - 4.0, - 2.4; p < 0.0001) for adherent patients and - 1.6 kg (95% CI - 2.5, - 0.8; p = 0.0001) for non-adherent patients. An increase in self-reported hypoglycaemic events (HEs) was observed, but no severe events were reported. Gastrointestinal disorders were the most common adverse effects. Among patients with available data on self-reported HEs (n = 216), 67 (31.0%) experienced HEs. The mean age, HbA1c levels and T2DM duration of patients with vs without HEs were 51.0 vs 53.3 years, 6.99 vs 6.66% and 9.2 vs 7.9 years. A greater proportion of patients experiencing HEs were treated with oral antidiabetic drugs like biguanides (90.6% vs 86.7%), sodium glucose cotransporter 2 inhibitors (85.9% vs 80.7%), sulfonylureas (32.8% vs 25.9%) and dipeptidyl peptidase 4 inhibitors (20.3% vs 11.1%). CONCLUSION: The O-SEMA-FAST study demonstrated that most participants adhered to oral semaglutide instructions and experienced significant reductions in HbA1c and body weight. Overall, baseline characteristics were similar regardless of HEs; however, patients reporting HEs were younger, had higher HbA1c levels, longer T2DM duration and were under polypharmacy. Oral semaglutide is a suitable choice for individuals who fast during Ramadan, effectively controlling glycaemic levels and managing body weight while maintaining a favourable safety profile. TRIAL REGISTRATION: NCT05716724.