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.

Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations

“…As noted, DKA due to the use of SLGT2 inhibitors has led to DKA in the absence of marked hyperglycemia reported in hospitalized patients (13,37), while in practice it remains relatively uncommon. Interestingly, euDKA was rarely reported in SGLT2i clinical trials (38).…”

Euglycemic Diabetic Ketoacidosis With COVID-19 Infection in Patients With Type 2 Diabetes Taking SGLT2 Inhibitors

“… 6 , 13 In a retrospective cohort study, patients with diabetes using SGLT2is had an odds ratio of 1.48 for DKA compared with nonusers, and 41% of these patients had a peak glucose level of <250 mg/dL compared with 0.8% of nonusers. 7 Known precipitating factors include acute illness with poor oral intake, vomiting, fasting, and reductions in insulin doses; 14 all our patients reported such factors.…”

Gender differences in adverse event reports associated with antidiabetic drugs

“…Two population-based studies are in line with our results. A study in Singapore using national adverse reporting data identified majorities of reports describing urinary tract infection involved female patients 23 . A retrospective cohort study using claim data in the United States, the excess risk per 1000 people for genital infection in the SGLT2i group comparing to the DPP4i group was greater in women than in men (87.6 vs. 11.9) 18 .…”