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

Kim, YG; Jeon, JY; Han, SJ; Kim, DJ; Lee, KW; Kim, HJ
Diabetes, obesity & metabolism, 20(8):1852-1858, 2018
Journal Title
Diabetes, obesity & metabolism
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.
antidiabetic drugcohort studydiabetes complicationsDPP-4 inhibitorSGLT2 inhibitor
MeSH terms
AdultAgedAged, 80 and overCohort StudiesDiabetes Mellitus, Type 2/bloodDiabetes Mellitus, Type 2/drug therapy*Diabetic Ketoacidosis/chemically inducedDiabetic Ketoacidosis/epidemiologyDiabetic Ketoacidosis/prevention & control*Diabetic Ketoacidosis/therapyDipeptidyl-Peptidase IV Inhibitors/adverse effectsDipeptidyl-Peptidase IV Inhibitors/therapeutic useFemaleFollow-Up StudiesHospitalizationHumansIncidenceInsurance, Health, ReimbursementKaplan-Meier EstimateMaleMiddle AgedProportional Hazards ModelsRepublic of Korea/epidemiologyRetrospective StudiesRiskSodium-Glucose Transporter 2 Inhibitors/adverse effectsSodium-Glucose Transporter 2 Inhibitors/therapeutic use*Young Adult
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
전, 자영한, 승진김, 대중이, 관우김, 혜진
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