Adjunct Dapagliflozin Improves Glycemic Control But Increases Ketoacidosis in T1D
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Dapagliflozin, when used as adjunct therapy to adjustable insulin in patients with type 1 diabetes, has been shown to improve glycemic control, according to clinical trial results published in Diabetes Care. In addition to the observed improvements in glycemic stability, dapagliflozin was also well-tolerated with no increase in hypoglycemia, though it increased the incidence of diabetic ketoacidosis.
Recently, a randomized, placebo-controlled trial (DEPICT-1) reviewed the efficacy and safety of dapagliflozin with adjunct insulin therapy in patients with type 1 diabetes. In order to provide further supportive evidence to that study, researchers initiated the current trial (DEPICT-2; NCT Identifier: NCT02460978). To conduct a phase 3 clinical trial evaluating the efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with poorly controlled type 1 diabetes, investigators enrolled 1465 individuals in the trial. After the lead-in period, 815 people were randomly assigned to either the dapagliflozin 5 mg plus insulin group (n=271), the dapagliflozin 10 mg plus insulin group (n=270), or the placebo plus insulin group (n=272). Most participants (87.9%-90.7%) in each group completed the study.
Results revealed that dapagliflozin offered significant improvements in glycemic control at 24 weeks (P <.0001). Dapagliflozin also significantly improved "mean glucose levels, glycemic variability, and time in glycemic target range" (P <.0001 for all). Dapagliflozin was also shown to significantly decrease body weight and total daily insulin dose (P <.0001). Compared with placebo, dapagliflozin treatment was well-tolerated with hypoglycemia balanced between groups. More patients using dapagliflozin had HbA1c reduction of ≥ 0.5% compared with placebo (P <.0001). However, the researchers found that there were more adjudicated definite diabetic ketoacidosis events with dapagliflozin.
Study limitations include that the 24-week time period only provided a short-term data perspective regarding the clinical benefits and risks associated with dapagliflozin. Another limitation was that the trial did not use the insulin titration algorithm mandated in real-world situations.
The investigators note that the study, "strengthens the weight of evidence that dapagliflozin could play an important role in the management of type 1 diabetes, helping to address several important unmet treatment needs, including improved glycemic control with decreased glycemic variability, weight loss, and decrease in insulin dose."
This study was funded by AstraZeneca and Bristol-Myers Squibb. Please refer to reference for a complete list of authors' disclosures.
Mathieu C, Dandona P, Gillard P, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 Study): 24-week results from a randomized controlled trial [published online July 19, 2018]. Diabetes Care. doi: 10.2337/dc18-0623