SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and during Hospital Admission

Peter S. Hamblin, Rosemary Wong, Elif I. Ekinci, Spiros Fourlanos, Sonali Shah, Alicia R. Jones, Matthew J.L. Hare, Genevieve L. Calder, Dilan Seneviratne Epa, Elizabeth M. George, Rinky Giri, Mark A. Kotowicz, Mervyn Kyi, Nicole Lafontaine, Richard J. Macisaac, Brendan J. Nolan, David N. O'Neal, Debra Renouf, Suresh Varadarajan, Jennifer WongSylvia Xu, Leon A. Bach

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


Context Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). Objective To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. Design Retrospective, multicenter, controlled cohort study. Setting All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. Patients Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes Main Outcome Measures In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. Results There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). Conclusions SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.

Original languageEnglish
Pages (from-to)3077-3087
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Issue number8
Publication statusPublished - 19 Jun 2019
Externally publishedYes


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