medwireNews: Real-world, off-label sodium–glucose cotransporter (SGLT)2 inhibitor use is uncommon in people with type 1 diabetes but appears to be associated with a higher than expected rate of diabetic ketoacidosis (DKA) when compared with clinical trials, US researchers report.
Christian Hampp (US Food and Drug Administration [FDA], Silver Spring, Maryland) and team found that the rates of DKA were particularly high among young women.
Using data from the FDA’s Sentinel System, which includes claims information for over 100 million patients, Hammp and team identified 475,527 individuals who initiated an SGLT2 inhibitor between March 2013 and June 2018.
And despite the fact that, to date, no SGLT2 inhibitor has been approved by the FDA for the treatment of type 1 diabetes, 0.92% of these patients met broad criteria for having type 1 diabetes (>50% of diagnosis codes specific to type 1 diabetes in the 1-year baseline period).
In addition, 0.50% met narrow criteria for type 1 diabetes, which comprised the broad criteria plus at least one prescription for insulin and none for an oral antidiabetic drug other than metformin.
The researchers report in Diabetes Care that the proportion of patients initiating SGLT2 inhibitors “was highly age dependent.” For example, 14.0% and 10.8% of patients initiating canagliflozin between the ages of 12 and 18 years met the broad and narrow criteria for type 1 diabetes, respectively. For those aged 65 years and older, the corresponding proportions were 0.72% and 0.24%.
During follow-up, the overall rates of DKA in the broad and narrow groups were 4.5 and 7.3 cases per 100 person–years, respectively, and were higher among women than men (6.0 and 8.9 vs 3.2 and 5.8 cases per 100 person–years, respectively).
The highest rate of DKA was observed among women aged 25–44 years who met the narrow criteria for type 1 diabetes, at 19.7 cases per 100 person–years. Among the men meeting the same criteria, the highest rate of DKA occurred in the same age group, but was less than half of that for women, at 8.7 cases per 100 person–years.
By comparison, the rates of DKA among more than 350,000 people who initiated an SGLT2 inhibitor for type 2 diabetes during the same period was 0.41 cases per 100 person–years.
And when the researchers used age- and sex-specific DKA incidence rates from sotagliflozin trials 309, 310, and 312 to calculate the standardized incidence ratios (SIRs) for the Sentinel population, they found that the DKA rate was 1.83-fold higher among individuals aged 25 years and older who met the narrow criteria for type 1 diabetes than would be expected based on the clinical trial data.
Furthermore, the “SIRs decreased with increasing age, suggesting a larger discrepancy in observed vs. expected events in younger patients,” Hammp et al remark.
Indeed, the largest discrepancy was observed for individuals aged 25–44 years meeting the narrow type 1 diabetes criteria. These individuals had a DKA rate that was 2.6-fold higher than expected.
However, the investigators point out: “Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs.”
By Laura Cowen
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