SGLT2 inhibitors for primary prevention of macrovascular and major microvascular complications in type 2 diabetes: an island-wide cohort study

OBJECTIVE: This study aimed to evaluate the different risks of developing cardiovascular disease and major microvascular complications between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and non-SGLT2i users in patients with type 2 diabetes (T2D) who do not have existing macrovascular or microvascular diseases. DESIGN: This study employed a retrospective, population-based cohort study design. SETTING: Data were obtained from Taiwan's National Health Insurance Research Database, covering the period from January 1, 2008, to December 31, 2021. Propensity score matching was used to identify 91,327 matched pairs of SGLT2 inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor users, 91,673 pairs of SGLT2 inhibitor and sulfonylurea users, and 20,857 pairs of SGLT2 inhibitor and glucagon-like peptide-1 receptor agonist (GLP-1 RA) users. PARTICIPANTS: The study included 1,145,035 patients diagnosed with T2D from the NHIRD. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to assess the risk of outcomes. RESULTS: SGLT2i users showed a lower risk of coronary artery disease (0.80 (0.73-0.87), 0.78 (0.72-0.85) and 0.74 (0.64-0.86)), heart failure (0.44 (0.38-0.49), 0.56 (0.50-0.62) and 0.66 (0.55-0.78)), cardiovascular death (0.47 (0.40-0.56), 0.47 (0.40-0.55) and 0.68 (0.53-0.87)), dialysis (0.03 (0.02-0.05), 0.13 (0.10-0.17) and 0.16 (0.11-0.23)), vision-threatening retinopathy (0.58 (0.51-0.67), 0.59 (0.51-0.67) and 0.78 (0.62-0.98)), amputation (0.29 (0.20-0.41), 0.28 (0.21-0.38) and 0.61 (0.46-0.89)) and all-cause mortality (0.42 (0.39-0.445), 0.39 (0.37-0.42) and 0.68 (0.61-0.76]))when compared to DPP-4 inhibitors, sulfonylureas, and GLP-1 RA users, respectively. CONCLUSIONS: This study showed that SGLT2i use was associated with a lower risk of incident cardiovascular diseases, major microvascular complications and mortality compared with the use of DPP-4 inhibitors, sulfonylureas and GLP-1 RA in patients with T2D, who did not have macrovascular and microvascular diseases.