Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Abstract

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide.

Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified.

Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% < 5 years), and a minority (15.6%) had a history of cardiovascular events. Importantly, oral semaglutide was started in subjects with various disease durations and background therapies. Notably, its initiation was accompanied by de-prescription of sulfonylureas, pioglitazone, DPP-4 inhibitors, and insulin. Choice of oral semaglutide was influenced by patient profiles and ongoing glucose-lowering regimens. Factors such as younger age, higher HbA1c, and ongoing SGLT-2 inhibitor therapy drove the choice of oral semaglutide with the aim of improving glycemic control. Projected glycemic effectiveness analysis revealed that oral semaglutide could potentially lead HbA1c to target in > 60% of patients, and more often than sitagliptin or empagliflozin.

Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management.

Keywords: Cardiovascular risk; GLP-1; Management; Survey; Therapeutic inertia; Type 2 diabetes.

Fig. 1

Patient phenotypes and trajectories by ongoing glucose-lowering regimen. Note: Arrows are reported when the difference between the reported variable in the specific group is significant compared to that in the remaining population. Bold arrows: significant vs overall with study-wide significance p < 0.0005; regular arrows: significant vs overall with nominal p < 0.05

Fig. 2

Reasons for choosing oral semaglutide by ongoing glucose-lowering regimen. Note: Arrows are reported when the difference between the reported variable in the specific group is significant compared to that in the remaining population. Arrows with asterisk: significant vs overall with study-wide significance p < 0.0005; regular arrows: significant vs overall with nominal p < 0.05

Fig. 3

Predicted improvements in HbA1c. Prediction of HbA1c reduction and achievement of different glycemic targets were calculated among 1869 patients using oral semaglutide only as add-on therapy. A Estimates done using data from RCTs (PIONEER 2,3,7). B Estimates done using data from the IGNITE real-world evidence (RWE) study. C Comparison of expected benefit (proportion of subjects achieving HbA1c < 7%) from the addition of oral semaglutide versus empagliflozin or sitagliptin, among n = 1259 subjects without SGLT-2 or DPP-4 inhibitors as background regimen