Exenatide improves glycaemic control, weight loss in uncontrolled T2D
Once-weekly doses of the glucagon-like peptide-1 receptor agonist exenatide plus insulin glargine improved glucose control and weight loss in patients whose type 2 diabetes (T2D) was uncontrolled on basal insulin and metformin, according to findings from the DURATION-7* trial.
“Patients receiving exenatide QW were twice as likely to have improved HbA1c and body weight than those treated with titrated insulin glargine alone,” said Dr Juan Pablo Frias from the National Research Institute, Los Angeles, California, US, who presented the findings at EASD 2017.
Patients recruited at screening (n=808) were individuals with uncontrolled T2D (HbA1c ≥7.5 to ≤12.0 percent; mean HbA1c 9.2 percent) on insulin glargine (≥20 U/day) with or without metformin and a sulphonylurea. Following an 8-week run-in period during which insulin glargine was titrated, 464 patients with HbA1c ≥7.0 to ≤10.5 percent (mean HbA1c, 8.5 percent) despite basal insulin and stable metformin (sulphonylurea use was discontinued) were randomized to receive exenatide QW (n=233, mean age 57.8 years, 49.4 percent male, mean baseline weight 93.3 kg) or placebo (n=231, mean age 57.6 years, 46.5 percent male, mean baseline weight 97.4 kg) in addition to titrated insulin glargine (mean, 50 and 52 U/day in the exenatide and placebo groups, respectively) for 28 weeks.
At week 28, about 25 percent more patients on exenatide reached the target glycaemic goal of HbA1c <7.0 percent compared with patients on placebo (p<0.001), with a more evident reduction in HbA1c in patients on exenatide vs placebo (-1.0 percent vs -0.3 percent; least squares [LS] mean change from baseline, -0.7 percent; p<0.001). Patients on exenatide also experienced a mean 1.1 kg weight loss at 28 weeks compared with patients on placebo who gained a mean 0.4 kg (LS mean change, -1.5 kg; p<0.001). [EASD 2017, abstract OP 01(3)]
Almost 20 percent (19.5 percent) more patients on exenatide than placebo achieved the composite of reaching glycaemic targets with no weight gain or incidence of major hypoglycaemia (p<0.001).
A greater proportion of patients on exenatide compared with placebo experienced HbA1c reductions of any amount (80.9 percent vs 59.7 percent) as well as any weight loss (62.3 percent vs 39.8 percent).
Adverse event (AE) and serious AE incidence was comparable between patients on exenatide and placebo (53.9 percent vs 57.6 percent and 4.7 percent vs 4.8 percent, respectively), while more patients on exenatide reported gastrointestinal events (15.1 percent vs 10.8 percent) and injection site-related AEs (7.8 percent vs 3.0 percent).
Hypoglycaemia incidence was comparable between patients on exenatide and placebo (29.7 percent vs 29.0 percent) and there was no incidence of severe hypoglycaemia in either group.
“Clinical benefits of combining exenatide QW with basal insulin included a reduction in HbA1c, with a greater percentage of patients achieving glycaemic targets, reduced body weight, and no increase in hypoglycaemia incidence or rate despite improved glycaemic control,” concluded Frias.