Trial shows HbA1c reduced, hypoglycemia and DKA similar across study participants.
Although antidiabetic agents have been developed to target type 1 diabetes mellitus (T1DM), many patients do not achieve glycemic goals. Inhibition of the sodium-glucose cotransporter 2 (SGLT2) reduces glucose toxicity, and improves insulin sensitivity and β-cell function. As the mechanism of action of SGLT2 inhibitors is different from other agents and completely insulin-independent, the use of these drugs might potentially be efficacious in combination with insulin therapy.
Dapagliflozin is a highly selective and reversible SGLT2 inhibitor. The DEPICT-1 trial—a randomized, double blind, parallel controlled, three-arm, phase 3, multicenter study—have evaluated the efficacy and safety of dapagliflozin as adjunctive therapy with insulin in patients with type 1 diabetes who have eratically high blood glucose. The study was done at 143 sites in 17 countries. Anyone ages 18-75 years who had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been treated with insulin for ≥12 months was eligible for this study.
A total of 833 participants were randomized (1:1:1) to receive add-on therapy with dapagliflozin 5 mg, dapagliflozin 10 mg, or placebo. 778 patients were assigned to the full analysis set for efficacy analyses (dapagliflozin 5 mg [n=259] vs dapagliflozin 10 mg [n=259] vs placebo [n=260]), the other 55 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]. Randomization was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c.
Mean baseline HbA1c was 8.53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set. At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo group (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was -0·42% [95% CI -0·56 to -0·28; p<0·0001] and for dapagliflozin 10 mg vs placebo was -0·45% [-0·58 to -0·31; p<0·0001]).
The most common adverse events included nasopharyngitis (14%[n=38] vs 12% [n=36] vs 15% [n = 39]), urinary tract infection (7% [n=19] vs 4% [n=11] vs 5% [n=13]), upper respiratory tract infection (5% [n=15] vs 5% [n=15] vs 4% [n=11]), and headache (4% [n=12] vs 6% [n=17] vs 4% [n=11]).
The incidence of hypoglycemia was reported in 79% of dapagliflozin 5 mg group [n=220] and 79% of dapagliflozin 10 mg group [n=235], compared with 80% of placebo group [n=207]. The incidence of severe hypoglycemia was seen in 8% [n=21], 6% [n=19], and 7% [n=19] of patients, respectively. In addition, diabetic ketoacidosis occurred in 1% of patients in the dapagliflozin 5 mg group, 2% of patients in the dapagliflozin 10 mg group, and 1% of patients in the placebo group.
- Both doses of dapagliflozin had a significant reduction in Hb1Ac compared to placebo.
- There were no significant differences in risk of hypoglycemia and diabetic ketoacidosis in both the dapagliflozin group and placebo group.
- Data from the DEPICT-1 trial showed that dapagliflozin is safe and effective as an add-on to insulin agents in patients with T1DM.
Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschöpe D, Thorén F, Xu J, Langkilde AM. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomized controlled trial. Lancet Diabetes Endocrinol. 2017 Sep 13.
Kay Lynn Tran, Doctor of Pharmacy Candidate: Class of 2018; LECOM College of Pharmacy