Experience with Oral Semaglutide in Clinical Practice: Efficacy and Safety Data from the Multicentric Croatian Study

Abstract

Background: Oral semaglutide is the first oral GLP-1 receptor agonist approved for treating patients with type 2 diabetes mellitus (T2DM). This real-world retrospective study evaluated its effectiveness and tolerability in patients requiring a third-line antidiabetic agent due to poor glucoregulation. Methods: Adult patients with T2DM who were taking oral semaglutide and were monitored at tertiary diabetes centers in Croatia were identified through electronic medical records between October 2022 and December 2024. Patients’ data were included in the analysis if they had been on oral semaglutide for at least six months. Results: A total of 163 patients (72 females and 91 males) were recruited, with 96.9% classified as overweight or obese. Among them, 145 had a BMI greater than 30 (mean BMI: 34.18 ± 4.60). The addition of oral semaglutide to their treatment regimen resulted in significant reductions in BMI, HbA1c, and both postprandial and fasting blood glucose levels, as well as in AST and ALT levels (all p < 0.05). There was also an increase in HDL levels (p = 0.007). The side effects observed were consistent with those previously recognized. Conclusions: This study demonstrates that oral semaglutide is safe and effective for glycemic and extraglycemic management in a real-world setting when used as a third-line agent. The best outcomes in terms of weight and HbA1c reduction can be expected when it is introduced early, ideally within the first five years of diabetes duration, and particularly in patients who are insulin naive.