medwireNews: Sotagliflozin may be an effective add-on therapy to insulin for patients with type 1 diabetes, but the benefits are less clear in a young adult population, suggest the results of two studies presented at the EASD annual meeting in Lisbon, Portugal.
In accordance with the global inTandem3 trial results, the phase III inTandem2 study found that the sodium–glucose cotransporter (SGLT) 1 and 2 inhibitor improves glycemic control relative to placebo among insulin-treated type 1 diabetes patients in Europe and Israel.
As presented by Thomas Danne (Kinder-und Jugendkrankenhaus, Hannover, Germany), the inTandem2 investigators randomly assigned 782 adult patients to receive treatment with either sotagliflozin at a dose of 200 mg or 400 mg once daily or placebo, in addition to optimized insulin therapy.
Patients in both the 200 mg and 400 mg sotagliflozin groups had a significantly greater decrease in glycated hemoglobin (HbA1c) levels from baseline to week 24 than those in the placebo group, with corresponding least squared mean (LSM) decreases of 0.52%, 0.52%, and 0.12% from baseline values of 7.7%, 7.7%, and 7.8%, respectively.
Patients receiving sotagliflozin also experienced significantly greater weight loss and reduction in daily bolus insulin than those in the placebo group at week 4, and these differences were sustained until week 24.
Treatment-emergent adverse events (TEAEs) were reported in 55.9% of the 261 participants in the 200 mg group, 55.9% of 263 patients in the 400 mg group, and 51.4% of 257 in the placebo group. Two participants died over the course of the study, both from the placebo arm. There was a “slight increase” in diarrhea among patients receiving 200 mg or 400 mg sotagliflozin compared with placebo (5.4 vs 7.2 vs 3.9%).
Danne also noted that patients receiving sotagliflozin were more likely to experience diabetic ketoacidosis than those in the placebo group, with positively adjudicated rates of 0.8% and 1.5% in the 200 mg and 400 mg groups, respectively, compared with no cases in the placebo arm. However, he said that ketoacidosis rarely led to discontinuation of the study drug.
These results were consistent with the findings of the inTandem1 study, and “I have high hopes that in the right hands, of able physicians such as those sitting in this room, [sotagliflozin] might be a treatment option for patients with type 1 diabetes,” said Danne.
The results of the phase II JDRF study, however, found that the addition of sotagliflozin 400 mg to background insulin treatment did not significantly improve HbA1c levels at week 12 among young adults aged 18–30 years who had poorly controlled type 1 diabetes.
“This study was designed to specifically evaluate the dual SGLT1 and SGLT2 inhibitor sotagliflozin in patients with high unmet need,” Paul Strumph (Lexicon Pharmaceuticals Inc, The Woodlands, Texas, USA) told delegates.
“We defined that as patients with a high [Hb]A1c and patients who were young,” he explained.
Mean baseline HbA1c levels were 9.9% for the 40 patients randomly assigned to receive sotagliflozin alongside insulin treatment, and 9.7% among the 34 participants in the placebo group, decreasing to corresponding measurements of 8.4% and 8.7% at week 12.
These findings translated into LSM decreases of 1.33% for sotagliflozin-treated patients, and 0.99% for those in the placebo group, a nonsignificant difference, meaning that the primary efficacy endpoint was not met, said Strumph.
However, patients in the sotagliflozin group experienced a decrease in bodyweight from baseline to week 12, with an LSM decrease of 0.6 kg, compared with an increase of 1.8 kg for placebo-treated patients. Those in the sotagliflozin group also spent more time in the target glucose range of 3.9–10.0 mmol/L at week 12 (43.6 vs 32.9%), but this difference did not reach statistical significance.
In all, 58% of patients in the sotagliflozin group and 62% of those in the placebo group experienced treatment-emergent adverse events, and a corresponding 4.7% and 7.1% had serious adverse events. Only one patient, from the placebo group, experienced positively adjudicated diabetic ketoacidosis over the study period, and serious hypoglycemic events occurred in 2.3% of participants receiving sotagliflozin and 4.8% of those in the placebo group.
Summarizing the findings, Strumph said that the primary efficacy endpoint was not met in this 12-week study of sotagliflozin “in high-risk patients with elevated [Hb]A1c,” but the secondary endpoints suggested a “positive net benefit” of sotagliflozin.
“There was diabetic ketoacidosis, but it did not occur on sotagliflozin,” he concluded.
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