Adjunct Dapagliflozin Improves Glycemic Control But Increases Ketoacidosis in T1D

Investigators examined safety and efficacy of adjunct therapy to insulin for patients with type 1 diabetes who are not adequately controlled.

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.”

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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