The oral sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin had acceptable short-term tolerability when given as an adjunct to insulin in patients with type 1 diabetes, with expected increases in urinary glucose excretion seen with this class of drugs.
Although hypoglycemia was common, patients assigned to the study drug had reductions in 24-hour daily average blood glucose levels, glycemic variability, and mean percent change in total daily insulin dose, according to study results published in Diabetes Care..
Dapagliflozin, which is currently approved as an adjunct to diet and exercise in adults with type 2 diabetes, reduces glycemic levels by inhibiting the reabsorption of renal glucose independently of insulin. The efficacy of dapagliflozin and other SGLT2 inhibitors in patients with type 2 diabetes suggests that this oral therapeutic may provide a new option for patients with type 1 diabetes as well, according to researchers led by Robert R. Henry, MD, of San Diego Healthcare System.
The researchers designed this pilot study as a proof-of-concept study to test the safety and tolerability of dapagliflozin in this patient population. The study included 62 adults with type 1 diabetes who had an HbA1c of 7% to 10%. Patients were randomly assigned to one of four dapagliflozin doses or placebo for 2 weeks. All patients were also receiving stable doses of insulin.
At least 60% of patients in all the treatment groups reported at least one hypoglycemic event during the study period; however, only one of these events was considered a major event. The researchers observed no relationship between the assigned dose of the study drug and the rates of hypoglycemia.
No difference in the 7-point glucose monitoring levels was found for patients assigned to either placebo or dapagliflozin. There was a mean reduction of 2.29 mmol/L for 24-hour daily average blood glucose levels in patients administered dapagliflozin 10 mg. In addition, dapagliflozin 10 mg was associated with a 3.77 mmol/L reduction for mean amplitude of glycemic excursion and a reduction of 16.2% for the mean percentage change in total daily insulin dose.
Patients assigned to receive placebo also had reductions in some of the efficacy parameters. Specifically, they had a mean reduction of 1.13 mmol/L in 24-hour average blood glucose levels and a 0.45 mmol/L reduction in mean amplitude glycemic excursion.
The researchers did note that the 95% confidence intervals of the mean for all dapagliflozin doses overlapped with those for placebo, but added that the study was not designed to test for between-group differences for the efficacy parameters.
“Given the uncertain safety risks of using an SGLT2 inhibitor in the treatment of type 1 diabetes, additional measures to ensure patient safety were necessary, such as very close monitoring in an in-patient setting with guidance on insulin dose adjustments,” the researchers wrote. “These features of the study design may have contributed to improvement in glucose control in all patients, including patients receiving placebo for whom reduction in glucosuria occurred.”
This study was supported by AstraZeneca and Bristol-Myers Squibb. Medical writing and editorial assistance for the study was funded by AstraZeneca and Bristol-Myers Squibb.
Henry RR, Rosenstock J, Edelman S, et al. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2014;doi:10.2337/dc13-2955.