SGLT-2 inhibitors associated euglycemic and hyperglycemic DKA in a multicentric cohort

Abstract

Euglycemic diabetic ketoacidosis (EuDKA) secondary to Sodium-glucose co-transporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2D) is a rare but increasingly reported phenomenon. Not much is known about the burden of EuDKA in patients on SGLT2i or the associated factors. This retrospective cohort study tries to delineate the differences in factors associated with the development of EuDKA as compared to hyperglycemic DKA. We conducted a multicentre, retrospective study across three tertiary care centers under Weill Cornell affiliated-Hamad Medical Corporation, Qatar. The cohort comprised of T2D patients on SGLT2i who developed DKA between January 2015 to December 2020. The differences between the subjects who developed EuDKA or hyperglycaemic DKA (hDKA) were analyzed. A total of 9940 T2D patients were on SGLT2i during 2015–2020, out of which 43 developed DKA (0.43%). 25 developed EuKDA, whereas 18 had hDKA. The point prevalence of EuDKA in our cohort was 58.1%. EuDKA was most common in patients using canagliflozin, followed by empagliflozin and Dapagliflozin (100%, 77%, and 48.3%, respectively). Overall, infection (32.6%) was the most common trigger for DKA, followed by insulin non-compliance (13.7%). Infection was the only risk factor with a significant point estimate between the two groups, being more common in hDKA patients (p-value 0.006, RR 2.53, 95% CI 1.07–5.98). Canagliflozin had the strongest association with the development of EuDKA and was associated with the highest medical intensive care unit (MICU) admission rates (66.6%). In T2D patients on SGLT2i, infection is probably associated with an increased risk of developing EuDKA. The differential role of individual SGLT2i analogs is less clear and will need exploration by more extensive prospective studies.

Characterization, management, and risk factors of hyperglycemia during PI3K or AKT inhibitor treatment

“…Rare incidence of euglycemia DKA has been reported with SGLT2 inhibitor use. 32 This experience and the existence of an additional case report in the literature suggest that DKA is rare but significant AE with this combination of therapies. 33 …”

Prolonged ketosis and glycosuria secondary to SGLT2 inhibitor therapy

“…Most cases of SGLT2 inhibitor‐associated euglycemic DKA resolve within a few days of treatment. 3 The product monograph of canagliflozin states that the elevation in urinary glucose excretion approaches baseline by approximately 3 days following discontinuation. 2 However, small studies suggest that SGLT2 inhibitor‐associated euglycemic DKA may take more than twice as long to resolve as classic DKA.…”

Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Who Underwent Surgery for Pancreatic Carcinoma: A Case Report

“…In 2015, several studies reported that SGLT2is might predispose ketoacidosis ( 13 ). A few cases treated with SGLT2is demonstrated an eu-DKA ( 14 – 16 ). However, SGLT2i-associated eu-DKA has not attracted much attention.…”