SGLT-2 inhibitors linked to more diabetic ketoacidosis vs. DPP-4 inhibitors or sulfonylureas
A retrospective study found that new users of sodium-glucose cotransporter-2 (SGLT-2) inhibitors developed diabetic ketoacidosis at a rate of about 6 per 1,000 person-years, compared to 4.3 or 4.5 per 1,000 person-years with dipeptidyl peptidase-4 (DPP-4) inhibitors or sulfonylureas, respectively.
Use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors was associated with an increased rate of diabetic ketoacidosis compared with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors or sulfonylureas, a retrospective study found.
Researchers used a U.S. database to conduct a new-user active comparator cohort study among adult patients with type 2 diabetes and private insurance who had one or more prescriptions dispensed for SGLT-2 inhibitors, DPP-4 inhibitors, or sulfonylureas between January 2013 and December 2019. The primary outcome was diabetic ketoacidosis, defined according to diagnosis codes on hospital admission. The researchers adjusted for confounders through propensity score matching. Results were published Feb. 11 by Diabetes Care.
A total of 85,125 users of SGLT-2 inhibitors and 85,125 users of DPP-4 inhibitors were included in the first matched cohort, and both groups had a median follow-up time of 131 days. Three hundred forty-three patients taking SGLT-2 inhibitors had diabetic ketoacidosis (6.0 events per 1,000 person-years) compared with 256 patients taking DPP-4 inhibitors (4.3 events per 1,000 person-years), for an adjusted hazard ratio (HR) of 1.63 (95% CI, 1.36 to 1.96). The second matched cohort had 72,436 patients taking SGLT-2 inhibitors (median follow-up time, 138 d) and 72,436 taking sulfonylureas (median follow-up time, 128 d). In the second matched cohort, 313 patients in the former group (6.3 events per 1,000 person-years) and 227 in the latter (4.5 events per 1,000 person-years) had diabetic ketoacidosis (adjusted HR, 1.56; 95% CI, 1.30 to 1.87).
Limitations of the study were the inclusion of insulin in the comparator group and no adjustment for certain variables (e.g., prior medication use, baseline comorbidities, and measures of health care utilization), the authors noted. They added that the results may not be generalizable to patients with type 2 diabetes who have governmental or no health insurance, among other limitations.
“These findings have important clinical implications for patients with type 2 diabetes. Diabetic ketoacidosis is a major complication of diabetes that can be life threatening. … Clinicians need to be vigilant about this safety signal,” the authors wrote.