SGLT2 inhibitors and the risk of ketoacidosis

Authors

• JE Blau
• SE Lock
• SI Taylor
• KI Rother

Abstract

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of oral diabetes medications. Case reports of diabetic ketoacidosis (DKA) in patients on SGLT2 inhibitor treatment have recently emerged. In May 2015, the FDA issued a warning based on 20 cases of DKA between March 2013 and June 2014, identified through the FDA Adverse Event Reporting System (FAERS) database. Purpose and Method: To further investigate the extent of this treatment-emergent event and to elucidate potential mechanisms, we queried FAERS for reports of “acidosis”, “DKA” and “ketosis” since January 2013. As a control cohort, we examined DKA cases reported with another class of oral hypoglycemic agents, dipeptidyl peptidase 4 (DPPIV) inhibitors since first-in-class FDA approval in October 2006. Results: We retrieved a total of 186 reports of acidosis (canagliflozin=138; dapagliflozin=41; empagliflozin=7). Analysis demonstrated an average age of 47.5 years, 48.9% female; 30% on concomitant insulin, and 16% reported as “off label”. We compared these results to 69 cases retrieved with DPPIV inhibitors (sitagliptin=47; saxagliptin=8; linagliptin=12; alogliptin=2) with an average age 59.8 years, 62.3% female; 8.6% on concomitant insulin, and none “off label”. Individualized risk assessments are underway to investigate plausible mechanisms, such as reduced insulin dosing, resulting in lipolysis and ketogenesis, increased glucagon secretion, and off label use in patients with type 1 diabetes. Conclusion: Diabetes treatment with SGLT-2 inhibitors is associated with an increased risk of DKA as documented by 186 reports in 28 months (compared to 69 cases on DPPIV inhibitors in 103 months).

Scientific Focus Area: Epidemiology

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