AIMS: To compare the risks of cardiovascular events and major microvascular complications associated with adding sodium-glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to insulin therapy in patients with type 2 diabetes (T2D).
METHODS: Using Taiwan's National Health Insurance Research Database (2008-2021), we identified 20,655 propensity score-matched pairs of SGLT2 inhibitor and DPP-4 inhibitor users, and 10,445 matched pairs of SGLT2 inhibitor and GLP-1 RA users, all receiving concurrent insulin therapy. Cox proportional hazards models were applied to assess outcome risks.
RESULTS: SGLT2 inhibitor use was associated with significantly lower risks of major microvascular complications compared to both DPP-4 inhibitors (adjusted hazard ratio [aHR] 0.37, 95% CI: 0.33-0.41) and GLP-1 RAs (aHR 0.57, 95% CI: 0.49-0.66). Compared with DPP-4 inhibitors, SGLT2 inhibitors also conferred a lower risk of major adverse cardiovascular events (aHR 0.57, 95% CI: 0.53-0.61) and all-cause mortality (aHR 0.42, 95% CI: 0.39-0.45).
CONCLUSIONS: In patients with T2D on insulin, adding SGLT2 inhibitors was associated with lower risks of cardiovascular events, major microvascular complications, and mortality compared to DPP-4 inhibitors, and lower risk of major microvascular complications compared to GLP-1 RAs.
