Use of sodium–glucose cotransporter 2 (SGLT2) inhibitors poses a slight but clinically insignificant risk of diabetic ketoacidosis (DKA) among patients with type 2 diabetes, newly published registry data from Denmark indicate.
The findings are published online in Diabetes Care by Majken Linnemann Jensen, PhD, of the Steno Diabetes Center Copenhagen, Gentofte, Denmark, and colleagues.
The US Food and Drug Administration has warned that SGLT2 inhibitors may lead to DKA and the European Medicines Agency said a year ago that the product information for SGLT2 inhibitors must be updated to note that DKA is a "rare" adverse event with the drug class, affecting up to one in 1000 patients.
The new data, from a nationwide retrospective cohort study in Denmark, indicate similarly — that in clinical practice, about one type 2 diabetes patient per 1000 taking SGLT2 inhibitors will be hospitalized with DKA, say the researchers.
While DKA is potentially life-threatening, especially in older people, "the excess risk associated with SGLT2 inhibitor treatment was…not significant and is hardly clinically relevant," Dr Jensen and colleagues note.
They followed patients with filled prescriptions for antidiabetes medications or a diagnosis of type 2 diabetes identified from 1995 to 2014, and included "calendar time" to avoid confounding, as SGLT2 inhibitors were introduced in Denmark only in December 2012.
The Danish figures in fact show that the incidence of DKA among both women and men has been decreasing, by 5.6% per year.
Among 415,670 patients with type 2 diabetes in the registry between 1995 and 2014, there were 4045 first DKA events in 3 million person-years, corresponding to a crude incidence rate of 1.34 per 1000 person-years.
After adjustment for sex, current age, calendar time, and diabetes duration, and relative to diabetes patients without pharmacological treatment, those with exposure to noninsulin glucose-lowering medications had a hazard ratio for DKA of 1.3. For insulin monotherapy, the hazard ratio was 6.0.
No DKA events were listed for SGLT2–inhibitor monotherapy (in 31 person-years).
For any treatment combination including SGLT2 inhibitors, there were six DKA events in a total 3811 person-years, corresponding to a nonsignificant hazard ratio of 1.6.
"This is the first study to estimate nationwide incidence of DKA in type 2 diabetes with 20 years of follow-up and 3 million person-years of observation combined with prescription data," say the authors. "DKA is a rare condition in type 2 diabetes with decreasing incidence."
Dr Jensen has received research support from AstraZeneca. Disclosures for the coauthors are listed in the paper.
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Diabetes Care. Published online March 10, 2017. Article
Medscape Medical News © 2017
Cite this: Registry Confirms Low Risk of DKA With SGLT2 Inhibitors in Diabetes - Medscape - Mar 21, 2017.
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