medwireNews: The DEPICT-1 and inTandem1 investigators have released their 52-week findings, revealing persistent reductions in glycated hemoglobin (HbA1c) with sodium-glucose cotransporter (SGLT)2 inhibition, but a slightly increased risk for diabetic ketoacidosis (DKA).
John Buse (University of North Carolina School of Medicine, Chapel Hill, USA) presented the inTandem1 findings at the ADA’s 78th Scientific Sessions in Orlando, Florida, USA. He reported that the “majority” of the benefits seen at 24 weeks were sustained at 52 weeks; the 263 patients taking sotagliflozin 200 mg and the 262 taking the 400 mg dose achieved respective 0.25% and 0.31% HbA1c reductions versus placebo (268 patients), which was a slight deterioration from the 0.36% and 0.41% seen at week 24.
Buse suggested that the worsening, which was also seen in the placebo group, might be explained by “fatigue” from insulin optimization – all patients had their insulin optimized before starting on sotagliflozin, resulting in an HbA1c reduction from 8.2–8.3% to 7.5–7.6%.
The researchers’ assessment of net benefit – HbA1c of less than 7.0% without severe hypoglycemia or DKA – was met by 26.2% and 32.4% of patients taking sotagliflozin 200 and 400 mg, respectively, compared with 19.0% of those taking placebo. Sotagliflozin-treated patients also maintained reductions in fasting glucose and BMI at 52 weeks.
There was, however, a “small but significant” increase in DKA among patients treated with sotagliflozin, at 3.4% and 4.2% versus 0.4%. Buse suggested this risk “can be potentially mitigated with proper education and ketone monitoring.”
There was also the expected increase in genital mycotic infections, but a numerically lower rate of severe hypoglycemia among the sotagliflozin groups, despite the lower HbA1c, at 6.5% for both, compared with 9.7% in the placebo group.
Also at the conference, the DEPICT-1 investigators reported the outcomes of the 747 type 1 diabetes patients who continued to take their randomized treatment for an additional 28 weeks. Their poster shows that although HbA1c levels in all groups trended upwards over time and there was a slight reduction in the effect of active treatment, a significant difference remained.
The reduction in HbA1c levels from baseline to 52 weeks was greater for patients taking dapagliflozin 5 mg and 10 mg than for those taking placebo, with respective differences of 0.33% and 0.36%. HbA1c levels were a corresponding 0.42% and 0.45% lower at the 28-week follow-up.
Bodyweight remained stable in the placebo group, while the dapagliflozin 5 mg group maintained their reduction from baseline and the 10 mg group had further weight loss, to give final reductions of 2.95% and 4.54%, respectively.
As expected, genital and urinary tract infections were more common in patients taking dapagliflozin than placebo, but fractures, renal impairment, and hypoglycemia were not.
However, similar to the sotagliflozin findings, DKA became more common in patients taking dapagliflozin, at rates of 4.76 and 3.67 per 100 patient–years for the 5 and 10 mg groups, respectively, versus 2.15 per 100 patient–years for the placebo group. The most common identified cause was a missed insulin dose.
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