Clinical characteristics and outcomes of diabetes-related ketoacidosis (DKA) in sodium-glucose co-transporter-2 inhibitor (SGLT2i) users with type 2 diabetes.

Aim: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) offer significant cardiorenal benefits for people with type 2 diabetes (PwT2D). However, concerns remain regarding their association with diabetes-related ketoacidosis (DKA). (1) To compare demographics, precipitating factors, biochemical features, management, and outcomes of acute DKA admissions between SGLT2i users (n = 267) and non-users (n = 793) with T2D. (2) To conduct a systematic review and meta-summary of published studies describing SGLT2i-associated DKA in T2D.

Methods: A retrospective cohort study analysed data from 18 UK hospitals (April 2018-March 2024), using standardised DKA protocols. Propensity score matching compared DKA episodes between SGLT2i users and non-users. In addition, a systematic review and meta-summary was performed including studies from PubMed, EMBASE, MEDLINE, Scopus, and Web of Science focusing on DKA in PwT2D treated with SGLT2i.

Results: Within the DEKODE cohort, 534 matched individuals were analysed. SGLT2i users had lower glucose, pH, and bicarbonate levels than non-users. SGLT2i was identified as the sole precipitant in 30.3% of cases. Despite lower admission glucose and more profound acidosis, both SGLT2i users and non-users had similar clinical outcomes including duration of DKA and length of hospital stay. In the meta-summary of 1024 cases of SGLT2 inhibitor-associated DKA from 247 studies, the median age was 54.6 years, with 49.7% male and a median diabetes duration of 10 years. Biochemical features included acidosis (median pH 7.1), elevated ketones (5.7 mmol/L), and modest hyperglycaemia (10.6 mmol/L). DKA typically developed after 2 months of SGLT2i use, with 21.1% requiring intensive care admission.

Conclusions: Despite lower admission glucose, more pronounced acidosis, and a higher incidence of hypokalaemia episodes, clinical outcomes were similar between the matched population of SGLT2i users and non-users. This may be attributed to earlier identification of euglycaemic DKA, timely intervention, as well as the distinct pathophysiological profile of SGLT2i-associated DKA. Improved education on risk factors and preventive strategies is warranted with SGLT2i therapy.