Effectiveness and safety of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: A nationwide population-based study

Aim: To examine the real-world cardiovascular effectiveness and safety associated with sodium-glucose co-transporter-2 (SGLT2) inhibitor compared with dipeptidyl peptidase-4 (DPP-4) inhibitor treatment in older adults with type 2 diabetes. Materials and Methods: In this retrospective cohort study, older adults with type 2 diabetes (aged >= 65 years) were identified in the Korean National Health Insurance Service database from September 2014 to December 2016. In total, 408 506 new users of an SGLT2 inhibitor or DPP-4 inhibitor were propensity score matched. Cox regression was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for outcomes of interest: hospitalization for heart failure (HHF), all-cause death, myocardial infarction, stroke, diabetic ketoacidosis (DKA), bone fracture, severe hypoglycaemia, genital infection and urinary tract infection (UTI). Results: Compared with DPP-4 inhibitors, new users of SGLT2 inhibitors had a lower risk of HHF (HR 0.86; 95% CI 0.76-0.97), all-cause death (HR 0.85; 95% CI 0.75-0.98) and stroke (HR 0.86; 95% CI 0.77-0.97), but a similar risk of myocardial infarction (HR 0.95; 95% CI 0.77-1.19). The risks of DKA, bone fracture and severe hypoglycaemia were similar between both groups, although genital infection (HR 2.44; 95% CI 2.22-2.67) and UTI (HR 1.05; 95% CI 1.00-21.11) were more frequent among new users of SGLT2 inhibitors compared with DPP-4 inhibitors. Conclusion: Our findings suggest that initiation of SGLT2 inhibitors offers cardiovascular disease protection and can be used safely in older adults with type 2 diabetes.

Automated summary

New users of SGLT2 inhibitors, compared with DPP-4 inhibitors, had a lower risk of hospitalization for heart failure, all-cause death, and stroke, but a similar risk of myocardial infarction. The risks of diabetic ketoacidosis, bone fracture, and severe hypoglycemia were similar between both groups, although genital infection and UTI were more frequent among new users of SGLT2 inhibitors.