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

Abstract

Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2i). To determine the incidence, characteristics and outcomes of DKA in SGLT2i-users vs non-users with type 2 diabetes. Retrospective, multi-center, controlled cohort study. All public hospitals in Melbourne and Geelong (combined population 5 million), Australia, from 1 September 2015 - 31 October 2017. Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. In SGLT2i users vs non-users: (i) Odds ratio of DKA developing during hospital admission and (ii) Incidence of DKA. 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 two (2%) non-SGLT2i users, (odds ratio 37.4 [95% CI 8.0-175.9], p<0.0001). The incidence of diabetic ketoacidosis was 1.02/1000 (95% CI 0.74-1.41/1000) in SGLT2i users vs 0.69/1000 (0.58-0.82/1000) in non-SGLT2i users (odds ratio 1.48 (1.02-2.15), p=0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dl (14 mmol/l) compared to one (0.8%) non-SGLT2i user (p<0.001). SGLT2i users were more likely to develop DKA as an inpatient compared to non-SGLT2i users. SGLT2i use was associated with a small, but significant increased risk of DKA.