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

Diabetes Obes Metab. 2021 Mar;23(3):682-691. doi: 10.1111/dom.14261. Epub 2020 Dec 15.


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.

Keywords: aged, cardiovascular diseases, dipeptidyl-peptidase-4 inhibitor, drug-related side effects and adverse reactions, sodium-glucose co-transporter-2 inhibitor, type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Humans
  • Retrospective Studies
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Symporters*


  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Symporters
  • Sodium
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose