Rationale. New-generation antidiabetic drugs (SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and dual GIP/GLP-1 receptor agonists) have transformed type 2 diabetes management, extending benefits beyond glycaemic control to cardiovascular and renal protection and weight management. In Italy, AIFA Note 100 redefined prescribing and reimbursement criteria for these classes, extending prescribing rights to GPs. This study describes the evolution of antidiabetic drug prescribing patterns in Tuscany (2016-2025), focusing on changes before and after Note 100's introduction and update, and integrates drug utilization data with adverse drug reaction (ADR) reports from the Italian National Pharmacovigilance Network (RNF).
Methods. The study has two phases: (1) a retrospective cohort analysis of drug utilization using Tuscany Region healthcare administrative data (ARS Toscana); (2) a pharmacovigilance analysis based on ADR reports from Tuscany within the RNF. The study population includes all individuals in the inhabitant registry with at least one dispensing of antidiabetic drugs of interest (DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, tirzepatide, and combinations) during 2016-2025, with at least 2 years of observation before the index date. For each Regional Health Areas (Central, North-West, South-East Tuscany), annual incident and prevalent users will be described, with demographic and clinical characteristics of new users, including comorbidities per Note 100, across three periods (pre-, during, and post-update Note 100). For pharmacovigilance, annual reporting rates and patient characteristics will be described, and adverse events classified.
Relevance. Findings will provide descriptive evidence on dispensing patterns of antidiabetic drugs in Tuscany following regulatory changes, highlight geographical differences among the three Health Areas, and identify potential safety signals related to utilization trends.