Prescription of SGLT-2 inhibitors alone or in combination with RAS-inhibitors in patients with diabetes mellitus and comorbid cardiovascular disease, chronic kidney disease or cardiorenal disease: a real-world evidence study from the REPOSI registry

Patients with diabetes mellitus and comorbid cardiovascular disease, chronic kidney disease or cardiorenal disease should be treated with sodium-glucose cotrasporter 2 (SGLT-2) inhibitors, alone or in combination with renin-angiotensin system (RAS) inhibitors, in order to reduce their cardiovascular and renal risk. We conducted a multicenter, retrospective, observational cohort study using data from the Italian REPOSI registry, including 1372 patients with diabetes aged ≥ 65 years hospitalized with cardiovascular diseases (heart failure or ischemic heart disease), chronic kidney disease or cardiorenal disease, between 2008 and 2024, with the purpose of analyzing the prescription in these patients of SGLT-2 inhibitors, alone or in combination with RAS-inhibitors, before and after the implementation of Note AIFA 100 in 2022. The prescription of SGLT-2 inhibitors alone and also their combination with RAS-inhibitors is scarce in patients with diabetes and cardiovascular, renal and cardiorenal comorbidities attending internal medicine and geriatric Italian wards, across all eGFR categories, with never users ranging from 96.9% to 98.9%. The regulatory implementation of “Nota AIFA 100” only modestly improved the prescription of SGLT-2 inhibitors in these elderly patients, the improvement being about 14% among never users. The scarce utilization of SGLT-2 inhibitors and their combination with RAS inhibitors is still of clinical concern, owing to the maximization of cardiorenal protection that stems from these drugs in patients with diabetes. The reclassification of SGLT-2 inhibitors in the group of products that can be reimbursed in pharmacies, adopted by AIFA in 2025, is expected to produce greater adherence to these important medications.