Sodium-glucose co-transporter-2 inhibitors and the risk of ketoacidosis in patients with type 2 diabetes mellitus: A nationwide population-based cohort study

Diabetes Obes Metab. 2018 Aug;20(8):1852-1858. doi: 10.1111/dom.13297. Epub 2018 Apr 14.


Aims: To estimate the risk of diabetic ketoacidosis (DKA) associated with sodium-glucose co-transporter-2 (SGLT2) inhibitor treatment compared with the risk associated with dipeptidyl-peptidase-4 (DPP-4) inhibitor treatment.

Methods: A nationwide population-based cohort study using claims data from the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed. A total of 56 325 patients who were started on SGLT2 inhibitors were included in this study and were matched with same number of patients who were started on DPP-4 inhibitors using propensity score matching. Kaplan-Meier curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for DKA.

Results: The risk of hospitalization for DKA was not increased in SGLT2 inhibitor users vs DPP-4 inhibitor users (hazard ratio [HR] 0.956, 95% confidence interval [CI] 0.581-1.572; P = .996). The incidence rate of hospitalization for DKA during the first 30 days after initiation of the SGLT2 inhibitor was 2.501 cases per 1000 person-years, which was higher than the rate during 3 years (0.614 cases per 1000 person-years). SGLT2 inhibitor use was associated with a higher HR in patients with diabetic microvascular complications (HR 2.044, 95% CI 0.900-4.640; P = .088) and in patients taking diuretics (HR 3.648, 95% CI 0.720-18.480; P = .118), although these associations were not statistically significant.

Conclusion: We found that SGLT2 inhibitor treatment did not increase the risk of DKA compared with DPP-4 inhibitor treatment. Our findings suggest that patients prescribed diuretics or those with microvascular complications may have a greater tendency to be hospitalized for DKA.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; antidiabetic drug; cohort study; diabetes complications.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Ketoacidosis / chemically induced
  • Diabetic Ketoacidosis / epidemiology
  • Diabetic Ketoacidosis / prevention & control*
  • Diabetic Ketoacidosis / therapy
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Female
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Incidence
  • Insurance, Health, Reimbursement
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Young Adult


  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors