On-label SGLT2 inhibitor use in T1D aggravates diabetic ketoacidosis risk

On-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors seems to worsen the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D), a new study has found.

Researchers conducted a real-world, retrospective, observational analysis of 11,475 T1D patients on insulin medication; participants were enrolled from the Japanese Medical Data Vision database. SGLT2 inhibitors were prescribed in 1,898 participants, yielding a rate of 16.5 percent. Cox multivariate regression analyses were performed to estimate DKA risk in these patients.

A total of 823 cases of DKA were recorded, resulting in an occurrence rate of 7.2 percent in the overall sample, which was slightly higher in the subgroup of patients prescribed with SLGT2 inhibitors (7.3 percent vs 7.1 percent).

In terms of incidence, DKA developed at a rate of 9.68 per 100 person-years in the overall cohort and was more than twice greater in those taking SGLT2 inhibitor medications (20.2 vs 8.7 per 100 person-years). Kaplan-Meier curves showed that over 334 days of observation, DKA developed significantly more frequently in these patients (p<0.001).

Correspondingly, the risk estimate of DKA was significantly higher in patients taking SGLT2 inhibitors (hazard ratio [HR]. 1.66, 95 percent confidence interval [CI], 1.33–2.06; p<0.001). Sex had no clear effect on the risk analysis, while the effect of SGLT2is on DKA seemed to be attenuated in older participants.

“Following these findings, we emphasize anew the importance of proper ‘on-label’ use of SGLT2 inhibitors in insulin-treated T1D patients to minimize DKA risk,” the researchers said.