PS. Hamblin, R. Wong, EI. Ekinci, S. Fourlanos, S. Shah, AR. Jones, MJL. Hare, GL. Calder, DS. Epa, EM. George, R. Giri, MA. Kotowicz, M. Kyi, N. Lafontaine, RJ. MacIsaac, BJ. Nolan, DN. O'Neal, D. Renouf, S. Varadarajan, J. Wong, S. Xu, et al. (2019). SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and During Hospital Admission. The Journal of clinical endocrinology and metabolism, 104(8), 3077-3087. https://doi.org/10.1210/jc.2019-00139

PubMed 30835263

[Abstract]
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.