Long-Term Efficacy and Safety of Dapagliflozin for Type 1 Diabetes
The results from this full 52-week study of dapagliflozin in T1D consist of a 24-week double-blind short-term period plus a 28-week extension period with blinded subjects and study sites.
According to study results published in Diabetes Care, patients who received 52 weeks of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, for type 1 diabetes (T1D) had significant improvements in glycemic control and weight loss but were more likely to experience diabetic ketoacidosis than patients receiving placebo.
To determine the efficacy and safety of dapagliflozin, researchers conducted a multicenter, placebo-controlled phase 3 trial in which 833 patients with inadequately controlled T1D were randomly assigned to receive either 5 mg or 10 mg of dapagliflozin or placebo for 1 year.
To measure efficacy, patients were assessed for changes in glycated hemoglobin (HbA1c) from baseline to 52 weeks, as well as percentage change from baseline in daily insulin dose and body weight. The 5-mg group had an adjusted mean change in HbA1c levels of -0.27% (average HbA1c at 52 weeks, 8.2%), compared with -0.31% in the 10-mg group (8.2%) and 0.06% in the placebo group (8.5%). Likewise, patients receiving the 5-mg dapagliflozin dose lost on average 2.95% more body weight than patients in the placebo group and patients in the 10-mg group lost 4.54% more. Compared with the placebo group, total insulin dose/day decreased in both the 5-mg and 10-mg dapagliflozin treatment groups by week 2 and remained lower throughout the course of the study.
The researchers reported no significant changes in vital signs and electrocardiogram data in any group at 52 weeks. However, 13.4% of patients in the 5-mg group reported experiencing serious adverse events compared with 13.5% in the 10-mg group and 11.5% in the placebo group.
Hypoglycemia events occurred at a similar rate in all groups, but diabetic ketoacidosis was significantly more common in the 5-mg and 10-mg dapagliflozin groups than the placebo group (4% and 3.4% vs 1.9%, respectively). However, the researchers reported that all events of diabetic ketoacidosis were successfully managed with standard care.
The researchers noted limitations to their study, including that insulin was not titrated using a protocol-mandated algorithm, which could prevent the full potential of dapagliflozin for glycemic control.
According to the researchers, dapagliflozin “was well tolerated and led to a clinically relevant improvement in glycemic control and weight loss, without additional risk for hypoglycemia and with a reduction in daily insulin dose which helps to resolve major problems around metabolic control in type 1 diabetes.”
Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study [published online October 23, 2018]. Diabetes Care. doi:10.2337/dc18-1087