Individual SGLT2 Inhibitors and the Risk of Diabetic Ketoacidosis

SGLT2 inhibitors (SGLT2i) are increasingly prescribed to treat type 2 diabetes (T2D) given their cardiovascular benefits. However, SGLT2i are known to increase the risk of diabetic ketoacidosis (DKA) , a rare yet serious outcome. It remains unclear whether individual SGLT2i are associated with a differential risk of DKA. Using 3 US healthcare claims databases (1/2014 - 12/2020) we assembled 2 cohorts of adults with T2D initiating (1) individual SGLT2i, i.e., canagliflozin, dapagliflozin, or empagliflozin, for a within-class comparison between SGLT2i (cohort #1, median age=62 years, 55% male) , and (2) individual SGLT2i or dulaglutide, for comparisons between SGLT2i and an out-of-class comparison (cohort #2, median age=63 years, 54% male) . Cohorts were reweighed using inverse probability of treatment weights, accounting for >130 baseline patient characteristics. Hazard ratios (HRs) and 95% CIs were estimated for hospitalization for DKA in each database and pooled using random-effects models. Over a median follow-up of 6 months, neither empagliflozin [HR (95% CI) = 0.96 (0.78-1.19) ], or dapagliflozin [HR (95% CI) = 0.76 (0.58-1.01) ] had a differential DKA risk vs. canagliflozin. All 3 SGLT2i were associated with a similar increase in DKA risk vs. dulaglutide (Table) . In this large cohort study, we found no difference in the risk of DKA across individual SGLT2i, but all SGLT2i types were associated with an increased risk of DKA vs. dulaglutide. Disclosure D.Abrahami: None. E.D'andrea: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. J.M.Paik: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20326)