Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature. Issue 1 (6th July 2017)

• Record Type: Journal Article
• Authors: Bonora, Benedetta Maria; Avogaro, Angelo; Fadini, Gian Paolo
• Is Part Of: Diabetes, obesity & metabolism. Volume 20:Issue 1(2018)
• Page Start: 25
• Page End: 33
• Publication Date: 2017-07-06
• Subjects: acute complications -- case reports -- clinical trials -- glucose‐lowering drugs -- pharmacovigilance; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13012
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i‐associated DKA and review the literature for similar cases within randomized controlled trials (RCTs), cohort studies and single reports. We searched the medical literature for reports of SGLT2i‐associated DKA cases. A quantitative analysis of frequency and clinical characteristics is reported. The 2 narrative cases illustrate that SGLT2i‐associated DKA can occur in patients with T1D incorrectly diagnosed as T2D, perhaps without the presence of obvious DKA precipitating factors. The incidence of SGLT2i‐associated DKA was less than 1/1000 in randomized controlled trials and 1.6/1000 person‐years in cohort studies. We retrieved detailed data on 105 SGLT2i‐associated DKA case reports, wherein 35% showed glucose levels of less than 200 mg/dL and 22% were not associated with typical triggers. In case reports and in pharmacovigilance databases, duration of SGLT2i treatment before DKA onset was extremely variable. Fatal SGLT2i‐associated DKA episodes were found only in pharmacovigilance databases and represented 1.6% of all reported cases. DKA is a rare adverse event during SGLT2i therapy. Predisposing and precipitating factors are still incompletely understood, although a minority of cases lacked typical DKA triggers. More narrative case series and cohort studies are needed to better understand the true risk and the spectrum of this adverse event.