Sharma Angelica, Ali Baig Shams, Thayakaran Rasiah, Rengarajan Lakshmi, Philip Nevil C, Abraham Anu Ann, Manta Aspasia, Narendran Parth, Dhatariya Ketan, Umpierrez Guillermo E, Kempegowda Punith
Department of Endocrinology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
Department of Applied Health Sciences, University of Birmingham, Birmingham, UK.
Diabetes Obes Metab. 2025 Sep 8. doi: 10.1111/dom.70098.
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.
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.
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.
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.
