An extension study of the phase 3 trial indicate combination therapy with exenatide and dapagliflozin was effective 104 weeks after randomization in patients with type 2 diabetes and inadequate glycemic control despite metformin therapy.
Results from an extension study of the DURATION-8 trial indicate the effect of combination therapy with dapagliflozin (Farxiga) and exenatide (Bydureon) on glucose control in patients with type 2 diabetes was still present after 2 years of continual use.
A 3-arm trial including 695 adult patients, results from the study suggest a therapeutic approach using the SGLT2 inhibitor and GLP-1 receptor agonist could work synergistically to help control blood glucose in type 2 diabetics.
"Many therapies in diabetes management are short-lived, which is why it's useful to test for long-term effect," says senior author Serge Jabbour, MD, director of the division of endocrinology and the Diabetes Center at Thomas Jefferson University, in a statement. "Our study showed that a combo regimen of dapagliflozin and exenatide continued to control patients' glucose for over two years. This is a very encouraging."
The original DURATION-8 trial was designed as a multicenter, double-blind, randomized, active-controlled, phase 3 trial with the goal of evaluating exenatide alone, exenatide plus dapagliflozin, or dapagliflozin alone in patients with type 2 diabetes and inadequate glycemic control despite stable metformin monotherapy.
With 52-week data from the original DURATION-8 trial concluding combination therapy with exenatide plus dapagliflozin resulted in greater control of HbA1c, fasting plasma glucose, and other parameters than exenatide or dapagliflozin alone, investigators sought to determine whether these effects were sustained 104 weeks after randomization.
Of the 695 patients who underwent randomization in the original trial, 431 completed treatment through 104 weeks. Analysis revealed adjusted leases squares mean change from baseline to week 104 was greater among patients receiving exenatide plus dapagliflozin (-1.70% [0.11]) versus exenatide alone (-1.29% [0.12]; P=.007) and dapagliflozin alone (-1.06% [0.12]; P <.001). Further analysis revealed clinically relevant changes in fasting plasma glucose, 2-hour postprandial glucose, body weight, and systolic blood pressure were observed among patients randomized to therapy with exenatide plus dapagliflozin.
In regard to safety, investigators observed no instances of major hypoglycemia, but noted episodes of minor hypoglycemia occurred in 4 patients randomized to combination and 1 patient in the dapagliflozin alone group. Additionally, more patients in the combination therapy group had episodes of other hypoglycemia (n=16) versus those randomized to exenatide alone (n=8) and dapagliflozin alone (n=8).
“The current long-term results of DURATION-8 add to the growing body of evidence that demonstrates the efficacy and safety of GLP-1RA plus SGLT2 inhibitor combination therapy and the durable effect of this combination,” noted investigators in their conclusion.
This study, “Efficacy and Safety Over 2 Years of Exenatide Plus Dapagliflozin in the DURATION-8 Study: A Multicenter, Double-Blind, Phase 3, Randomized Controlled Trial,” was published in Diabetes Care.