The addition of the SGLT-1 and -2 inhibitor sotagliflozin to usual insulin therapy can increase the proportion of patients with type 1 diabetes achieving a glycated haemoglobin level lower than 7.0%.
However treatment with the SGLT inhibitor came with an increased risk of diabetic ketoacidosis, according to a phase 3 trial of 1,400 patients across 133 sites and 19 countries including Australia.
The study found 28.6% of patients treated with sotagliflozin achieved the target HbA1c by week 24 with no severe hypoglycemia or diabetic ketoacidosis compared to 15.2% of the control group.
A sub-group analysis showed the effect was consistent in patients using pumps and those using other forms of insulin therapy.
Sotagliflozin also led to a meaningful reduction in bodyweight of about three kilograms.
There was no significant difference in severe hypoglycaemic events between the treated and control groups but rates of diabetic ketoacidosis were higher in treated patients who did not meet target HbA1c than controls (2.6 v 0.6%)
Professor Peter Colman, director of diabetes and endocrinology at Royal Melbourne Hospital and a study investigator, told the limbic there was need for adjunctive therapies but the increased risk of ketoacidosis would require careful management.
“There seemed to be slightly higher risk in patients on insulin pumps,” he said.
The study mitigated risks with information about the detection and treatment of ketosis, urogenital hygiene, proper hydration, and the use of urinary ketone strips and β-hydroxybutyrate meters and strips.
Professor Colman said a recent study of dapagliflozin did not show an increased risk of ketoacidosis.
“Sotagliflozin is a bit different than the other agents as it is a SGLT-1 and -2 inhibitor which involves change in the intestinal flux of glucose as well as the effect on the kidney SGLT so there is more research to be done in that context.”
“And the question is are the cardiovascular outcomes which are positively addressed in type 2 diabetes going to apply in type 1 diabetes?”
Professor Colman said the agent might be most useful in people who were concerned about their weight and those having difficult getting to the HbA1c target.
“I’m certainly enthusiastic about this treatment going forward but it is going to have to be handled with care. Ketoacidosis in people with type 1 diabetes is not to be taken lightly.”
An accompanying editorial in the NEJM said improved automated insulin delivery systems would ultimately achieve target HbA1c levels without additional risks.
The editorial said the possible benefit of lowering HbA1c, in terms of preventing microvascular disease, could not be balanced against the risk of ketoacidosis in such short-term studies.