DEPICT-1: Dapagliflozin a promising adjunct to insulin in T1D
Dapagliflozin improves glycaemic control with sustained weight loss without an increased risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) who are inadequately controlled with insulin, according to the DEPICT-1* study.
Dapagliflozin is a SGLT2** inhibitor previously approved for treating type 2 diabetes (T2D).
“SGLT2 inhibitors are the first class of antihyperglycaemic drugs to show the potential for cardiovascular and renal benefit [in T2D] … which is of particular importance in T1D, especially considering the younger age of presentation compared with T2D,” wrote the investigators.
The multinational, double-blind, phase III study randomized 833 patients (mean age 42.5 years, mean HbA1c 8.53 percent) with inadequately controlled T1D who had been on insulin for at least 1 year before study entry in a 1:1:1 ratio to receive oral dapagliflozin 5 mg or 10 mg once daily, or a matching placebo. [EASD 2017, session S27; Lancet Diabetes Endocrinol 2017;doi:10.1016/S2213-8587(17)30308-X]
At week 24, HbA1c was significantly reduced from baseline with both doses of dapagliflozin compared with placebo (difference in HbA1c change from baseline vs placebo, -0.42 and -0.45 percent for dapagliflozin 5 mg and 5 mg, respectively; p<0.0001 for both comparisons).
Total daily insulin dose was also significantly reduced at 24 weeks from baseline in both dapagliflozin arms vs placebo (difference vs placebo, -8.8 percent and -13.2 percent for dapagliflozin 5 mg and 10 mg, respectively; p<0.0001 for both).
Both dapagliflozin arms had significantly reduced body weight from baseline through week 24 compared with placebo (difference vs placebo, -2.96 percent vs -3.72 percent for dapagliflozin 5 mg and 10 mg, respectively; p<0.0001 for both).
“Dapagliflozin was well tolerated without an increase in either hypoglycaemia (mild or severe) or adjudicated DKA,” said lead author Dr Paresh Dandona of State University of New York at Buffalo in Buffalo, New York, US. Hypoglycaemia (79 percent and 79 percent vs 80 percent for dapagliflozin 5 mg and 10 mg vs placebo, respectively) and adjudicated DKA events (1 percent and 2 percent vs 1 percent) occurred in similar proportion of patients among the treatment groups.
More genital infections occurred in the dapagliflozin arms than the placebo arm, with the events being more common among women than men, although none of the cases were considered serious.
“DEPICT-1 therefore provides encouraging short-term data for the efficacy of adjunct SGLT2 inhibition in T1D, but might also provide insights into how the risk of ketoacidosis can be minimized,” wrote Dr John Petrie of University of Glasgow in Glasgow, UK, in a commentary. [Lancet Diabetes Endocrinol 2017;doi:10.1016/S2213-8587(17)30315-7]
“The investigators kept real-world clinical practice in mind by providing a very simple rule that insulin doses should be reduced by no more than 20 percent when study medication was started and that they should subsequently be titrated back towards the initial dose.”
“Based on the findings from DEPICT-1, adjunct therapy with SGLT2 inhibitors might be appropriate for individuals who have a good understanding of the early warning signs of ketoacidosis, undertake regular home monitoring (including of blood ketones), and have a high level of self-monitoring and communication with their diabetes team,” he added.
“Future studies, randomized and observational ones, will determine whether the use of this drug will help to decrease cardiovascular mortality in T1D,” said independent commentator Dr Maciej Malecki of Jagiellonian University Medical College in Kraków, Poland, during EASD 2017.