DEPICT-2 study of more than 800 people worldwide indicates positive results without added risk of severe hypoglycemia, but slight increase in DKA events.
Adding the selective SGLT-2 inhibitor dapagliflozin to intensive insulin therapy in adults with type 1 diabetes (T1D) who had sub-optimal diabetes management reduced glucose levels, aided in weight loss, and led to a reduction in insulin doses, yet also correlated with a slight increase in diabetic ketoacidosis risk compared to placebo, according to “Efficacy and Safety of Dapagliflozin in Patients with Inadequately Controlled Type 1 Diabetes—DEPICT-2 Study,” presented at the American Diabetes Association’s (ADA’s) 78th Scientific Sessions at the Orange County Convention Center.
Dapagliflozin is a selective inhibitor of SGLT-2, a protein responsible for glucose regulation. SGLT-2 inhibitors block the SGLT-2 protein involved in glucose reabsorption in the proximal renal tubule of the kidney, which results in an increase in renal glucose excretion and lower glucose levels.
DEPICT-2 was a phase 3, double-blind, global study conducted among 137 sites in North America, South America, Europe, and Asia to evaluate the efficacy and safety of dapagliflozin as an add-on to insulin therapy in people with T1D. The trial was similar in design to the DEPICT-1 study, which was published in September 2017.
DEPICT-2 enrolled 813 adults between the ages of 18 and 75 with T1D who had an HbA1c level from 7.5 to 10.5 percent. Patients were randomly assigned to receive daily, oral doses of either 5 mg of dapagliflozin (271 patients), 10 mg of dapagliflozin (270 patients), or a placebo (272 patients), in addition to their usual insulin, for 52 weeks. The insulin dose could be adjusted by clinicians based on the patient’s self-monitored glucose readings, local guidance, and individual circumstances.
This study evaluated patients after 24 weeks on the regimen, and the results showed that compared to placebo, patients treated with 5 mg and 10 mg of dapagliflozin had a decrease in HbA1c levels by .37 to .42 percent, respectively. The addition of dapagliflozin was also accompanied by weight loss, with the patients on 5 mg losing an average of 3.2 percent of their body weight, and the patients who received 10 mg losing 3.7 percent of their body weight, compared to an average weight loss of .02 percent in the placebo group. There was also a reduction in insulin doses in the dapagliflozin 5 mg and 10 mg group (-10.78 percent to -11.08 percent, compared to placebo). Continuous glucose monitoring showed more improved, stable glycemic values among dapagliflozin-treated patients, leading to an increased time-in-range over 24 hours of 2h 10min with dapagliflozin 5mg, and a little over 2h 30min with dapagliflozin 10mg, compared to placebo.
The safety analysis showed no significant increased risk of hypoglycemia, and in particular, severe hypoglycemia among patients treated with dapagliflozin: 17 patients (6.3 percent) from the dapagliflozin 5 mg group, 23 patients (8.5 percent) from the dapagliflozin10 mg group, and 21 patients (7.7 percent) from the placebo group experienced one or more episodes of severe hypoglycemia over the 24-week period. However, the dapagliflozin patients did have an increased risk of diabetic ketoacidosis (DKA), a known complication for patients with diabetes that affects those with type 1 more frequently than patients with type 2 diabetes. No patients from the placebo group experienced DKA, compared to 2.6 percent for the dapagliflozin 5 mg group and 2.2 percent for the dapagliflozin 10 mg group.
“The results of our study add to a growing body of evidence showing that SGLT-2 inhibitors have the potential to serve as promising adjunct therapies in people with T1D who are not consistently in their target blood glucose range,” said Chantal Mathieu, MD, PhD, professor of medicine at the Catholic University of Leuven, Belgium. “Results of the DEPICT-2 study were consistent with those of its twin study, DEPICT-1, which followed mostly European and American patients with type 1 diabetes. This new study had a greater global reach, with about a quarter of patients being from Asia. The benefits seen in both studies are important to people with T1D. Introduction of dapagliflozin as an adjunct therapy could be an interesting and exciting new treatment for T1D, almost 100 years after the discovery of life-saving insulin. However, adding dapagliflozin to the insulin regimen needs to be balanced against the increased risk of DKA, and this therapy should be coupled with intensive educational measures to cope with the small, but real risks.”
- One of the major benefits is the reduction of Insulin needed, and we know that less insulin required allows for better management.
- Adding dapagliflozin to insulin needs to be balanced against the increased risk of DKA, which requires intensive education.
- Dapagliflozin vs. Placebo as add-on to insulin in patients with T1D was well tolerated, improved glycemic management and decreased variability without increasing hypoglycemia, but with a slight increase in DKA events.
The study has been accepted for publication and will be featured in its entirety in an upcoming issue of Diabetes Care. ADA Scientific Meeting June 24, 2018