Adverse Drug Reaction Profile of SGLT2 Inhibitor-Associated Diabetic Ketosis/Ketoacidosis in Singapore and their Precipitating Factors.

ABSTRACT

BACKGROUND AND OBJECTIVE: As of December 2017, 20 diabetic ketosis (DK)/diabetic ketoacidosis (DKA) cases associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) had been reported to the Health Sciences Authority (HSA), Singapore. We aimed to provide a detailed analysis of the profile of these cases. METHODS: As part of the emerging safety issue monitoring, the HSA followed up on SGLT2i-associated DK/DKA cases with the reporters to obtain the missing and/or supplementary information. Descriptive statistics were employed to summarise the data collected, while the Mann-Whitney test was employed to evaluate the differences between typical and euglycaemic DKA cases as well as between genders. RESULTS: All cases led to hospitalisation but were non-fatal. Where reported, the majority (71-85%) of DK/DKA cases occurred within 180 days of SGLT2i therapy initiation and involved female patients and/or patients with long-standing type 2 diabetes mellitus (T2DM). Apart from the difference in blood glucose levels, no differences in the profile between the typical and euglycaemic DKA cases were noted. Known precipitating factors were identified in all cases. Acute illnesses, particularly infections and abscesses, were the most commonly reported precipitating factors, followed by insulin dose reduction/cessation. CONCLUSIONS: Based on the profile of the reported cases, it is imperative to maintain clinical vigilance for DK/DKA, especially during the first 6 months of SGLT2i treatment and more so in female patients and/or patients with long-standing T2DM. Prompt evaluation and management of underlying precipitating factors is also important to assess and mitigate the risk of developing DK/DKA during treatment with SGLT2i.