Once-weekly exenatide plus dapagliflozin was associated with clinically relevant improvements in glycemic control over a 2-year period compared with placebo, according to a study in Diabetes Care.
This study was the 104-week, multicenter, phase-3, DURATION-8 trial. Participants in this trial had type 2 diabetes and inadequate glycemic control, defined as an HbA1c of 8.0% to 12.0% (64–108 mmol/mol), despite stable metformin therapy of ±1500 mg/day for greater than or equal to two months prior to screening. The study investigators randomly assigned patients to once-daily 2m exenatide plus once-daily 10 mg dapagliflozin (n=228), once-daily exenatide plus placebo (n=227), or dapagliflozin plus placebo (n=230). The primary exploratory endpoint was the change in HbA1c from baseline to 104 weeks.
Approximately 62% (n=431) of patients initially enrolled completed the trial by 104 weeks. Patients who were randomly assigned to once-daily exenatide plus dapagliflozin had a greater adjusted least squares mean change in HbA1c from baseline to week 104 compared with once-daily exenatide plus placebo and dapagliflozin plus placebo (21.7% vs 21.3% vs 21.1%, respectively; P <.001).
Compared with treatment with once-daily exenatide plus placebo, treatment with once-daily exenatide plus dapagliflozin and without rescue therapy was associated with clinically relevant changes in fasting plasma glucose (between-group difference, 21.07; 95% CI, 21.71-20.42; P =.001), 2-hour postprandial glucose (between-group difference, 20.40; 95% CI, 21.26-0.46; P =.360), weight (between-group difference, 21.71; 95% CI, 22.95-20.47; P =.007), and SBP (between-group difference, 23.0; 95% CI, 25.7-20.2; P =.034).
Treatment with once-daily exenatide plus dapagliflozin and without rescue therapy was also associated with clinically relevant changes in fasting plasma glucose (between-group difference, 21.50; 95% CI, 22.16-20.85; P =.001) and 2-hour postprandial glucose (between-group difference, 21.23; 95% CI, 22.10-20.36; P =.006) compared with treatment with dapagliflozin plus placebo.
No unexpected safety findings were reported. Patients tolerated once-daily exenatide plus dapagliflozin well, and no episodes of major hypoglycemia were reported.
Limitations of the study included the high rate of patient withdrawal after 52 weeks as well as the exploratory nature of the analyses at 104 weeks.
Study authors concluded that further research is needed to determine whether the treatment combination “could potentially extend to a reduced incidence of cardiovascular and renal events in patients with type 2 diabetes.”
Disclosure: This clinical trial was supported by AstraZeneca. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Jabbour SA, Frías JP, Ahmed A, et al. Efficacy and safety over 2 years of exenatide plus dapagliflozin in the DURATION-8 study: a multicenter, double-blind, phase 3, randomized controlled trial. Diabetes Care. Published online August 18, 2020. doi: 10.2337/dc19-1350