SodiuM glucose cotrANsporter-2 (SGLT-2) inhibitors in the treatment of type II DiAbetes in Tuscany: utiLizatiOn patteRns, and relatEd clinical use evaluation; the MANDALORE study protocol

Background Diabetes mellitus is a globally prevalent disease, with an incidence of 5–7 new cases per 1000 person-years and no significant gender disparity. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are recommended as second-line therapy after metformin in uncomplicated type 2 diabetes, whereas they are recommended as first-line treatment in patients with heart failure or other cardiorenal comorbidities. Given the recent introduction of SGLT-2 inhibitors, their increasing utilization, and the heterogeneity of existing literature, real-world evaluations of these agents are warranted. Objectives The MANDALORE study, a regional active pharmacovigilance project approved by the Italian Medicines Agency (AIFA), aims primarily to assess the drug utilization of gliflozins in clinical practice. The secondary objective is to analyze safety outcomes and investigate the determinants of treatment switching events. Methods This retrospective cohort study will analyze medical records of patients who underwent at least one diabetes visit at the Metabolic Diseases and Diabetology/Endocrinology Unit of Pisa University Hospital and the Diabetology and Metabolic Diseases Unit of Livorno Hospital. Inclusion criteria comprise that Tuscan patients receiving their first prescription for a gliflozin (index drug) between 2012 and 2021 (index date). Outcomes to be assessed include treatment switching, time to switching, line of therapy, dose adjustments, and time to dose change. Gliflozin utilization will be investigated, particularly in relation to concomitant interacting or contraindicated medications, and in patients requiring caution as specified by AIFA labeling and relevant tools. Incidence rates will be calculated for secondary safety outcomes, including adverse drug events (ADEs) leading to emergency room visits or hospitalization, non-serious ADEs, and specific ADEs as diabetic ketoacidosis, urinary and genital infections, gangrene, lower limb amputations, and neoplastic events. ADEs and therapeutic effectiveness observed in proximity to switching events will be investigated. Results The findings from the MANDALORE study are expected to elucidate critical aspects of gliflozin use in routine clinical practice, particularly within the Tuscan regional healthcare context, thereby providing valuable insights from the real-world for clinicians and healthcare systems.