Sotagliflozin improves multiple outcomes in T1D patients on insulin
The addition of the sodium-glucose cotransporters 1 and 2 (SGLT1 and SGLT2) inhibitor sotagliflozin improved glycated haemoglobin levels, systolic blood pressure, and weight in patients with type 1 diabetes (T1D) on insulin therapy, according to findings of the InTandem3* trial presented at EASD 2017.
“Sotagliflozin added to insulin therapy can potentially help patients with T1D improve their glucose control and hopefully manage the disease with fewer complications,” said lead investigator Professor Satish Garg from the University of Colorado Denver, Aurora, Colorado, US.
“If long-term use continues to show similar metabolic improvements in patients with T1D, it is likely that the long-term complications of diabetes would be significantly reduced,” he said.
At week 24, more patients on sotagliflozin achieved an HbA1c of <7.0 percent compared with those on placebo with no incidence of severe hypoglycaemia or diabetic ketoacidosis (28.6 percent [n=200] vs 15.2 percent [n=107]; p<0.001). [EASD 2017, session S07; N Engl J Med 2017;doi:10.1056/NEJMoa1708337]
Compared with patients on placebo, patients on sotagliflozin also experienced greater changes from baseline in terms of body weight (difference, -2.98 kg), glycated haemoglobin levels (difference, -0.46 percentage points), and mean daily bolus insulin dose (-2.8 units/day; p<0.001 for all comparisons) at 24 weeks, as well as systolic blood pressure levels at 16 weeks among patients whose systolic blood pressure was ≥130 mm Hg at baseline (difference, -3.5 mm Hg; p=0.002).
Incidence of severe hypoglycaemia was comparable between patients on sotagliflozin and placebo (3.0 percent [n=21] vs 2.4 percent [n=17]; treatment discontinued in 2 and 1 patients, respectively), while incidence of diabetic ketoacidosis was higher among those on sotagliflozin (3.0 percent vs 0.6 percent; treatment discontinued in 11 and 1 patients, respectively).
According to the researchers, diabetic ketoacidosis may be especially likely among individuals using insulin pumps, highlighting the necessity of “closer monitoring” and potential substitution with basal insulin formulations in this group of patients.
Other adverse events included bone fractures (experienced by 4 and 5 patients on sotagliflozin and placebo, respectively) and genital mycotic infections (45 vs 15 patients).
InTandem3 was a global (133 centres in 19 countries), phase III, double-blind trial where 1,402 individuals with T1D with HbA1c 7–11 percent and BMI ≥18.5 kg/m2 were randomized to receive oral sotagliflozin (400 mg/day, n=699, mean age 43.3 years, 48.8 percent female) or placebo (n=703, mean age 42.4 years, 51.8 percent female) in addition to insulin therapy (dose adjusted to meet target blood glucose levels during self-monitoring) for 24 weeks.
However, Dr David Nathan from the Diabetes Center, Massachusetts General Hospital, Boston, Massachusetts, US, cautioned that the benefits of adjunctive treatments for T1D should be weighed against the risks. [N Engl J Med 2017;doi:10.1056/NEJMe1711296]
“[T]he results of this trial suggest that the increased risk of ketoacidosis counterbalances the increased likelihood of achieving a glycated haemoglobin level of less than 7 percent,” he said.
“[A]dvances in treatments for T1D have been aimed primarily at reducing the glycated haemoglobin level by improving the physiologic delivery of insulin with devices … [and] at developing insulin analogues that can be used to mimic the insulin profiles of nondiabetic patients.”
“The further development of automated insulin delivery systems is likely to make adjunctive drug therapies for T1D unnecessary … [by lowering] the glycated haemoglobin level while resulting in fewer episodes of hypoglycaemia than those seen with adjunctive therapies and requiring less effort from the patient,” said Nathan.