Use of the once-weekly receptor agonist exenatide (Byetta, Amylin/Eli Lilly) showed better glucose control in diabetic patients who have suboptimal glucose control and where body weight and hypoglycemia were of concern, compared to a treatment with insulin glargine (Lantus, Sanofi Aventis) injection, according to DURATION-3 trial results presented at the annual American Diabetes Association (ADA) conference in Orlando, Fla., and simultaneously published in the June 24 edition of the Lancet.
“Treatments are needed that are convenient, address both fasting and postprandial glucose control, reduce risk of hypoglycemia and avoid counterproductive side-effects (e.g., weight-gain),” the authors wrote. “A class of agents introduced within the past five years, the glucagon-like peptide-1 (GLP-1) receptor agonists, has the potential to address fasting and postprandial glucose control with weight loss and low risk of hypoglycemia.”
Michaela Diamant, MD, of the VU University Medical Centre in Amsterdam, and colleagues randomized 456 patients to either receive exenatide (233 patients) or insulin glargine (223 patients) between May 13, 2008, and May 19, 2009, at 72 sites.
During the phase III DURATION-3 clinical trial, researchers evaluated patients for 26 weeks after being placed on blood-glucose lowering regiments using changes in Hb1Ac levels as the primary endpoint.
Results showed that 21 percent of patients in the insulin glargine arm had a fasting glucose concentration in the range of 4 to 5.5 mmol/L. At 26 weeks, 6.8 percent of patients in the exenatide arm had glucose levels near 7 percent compared to 7 percent in the glargine arm.
Compared to baseline, at 26 weeks patients in the exenatide arm saw decreases of Hb1Ac levels of 1.5 percent, while those who received glargine saw decreases of 1.3 percent.
Overall, patients in the exenatide cohort achieved lower levels of Hb1Ac (less than 7 percent) compared with those who received glargine injection, 60 percent versus 48 percent, respectively. The percentage of those who reached Hb1Ac levels under 6.5 percent were 35 percent and 23 percent, respectively.
Results also showed that treatment with exenatide decreased body weight while insulin glargine significantly increased body weight in patients, -2.6 kg versus 1.4 kg.
Cases of hypoglycemia were reported in 8 percent of patients treated with exenatide and 26 percent treated with insulin glargine.
“Exenatide once weekly resulted in greater HbA1c reduction after 26 weeks of treatment than did insulin glargine titrated to target, and was associated with progressive body weight reduction,” the authors wrote.
A limitation to the study was the DURATION-3 trial’s open-label nature, which the authors said, could not exclude “a potential bias towards the novelty of a new promising treatment.”
They concluded, “Taken together, these findings showed that once-weekly exenatide resulted in greater reduction in HbA1c than did insulin glargine titrated to target, and is an important therapeutic consideration for patients for whom convenience, weight loss and risk of hypoglycemia are particular concerns."
In an accompanied editorial, Anoop Misra, MD, and Shashank Joshi, MD, of the Fotis Hospital in New Delhi, India, said, “A GLP-1 receptor analogue might be suitable in at least two subgroups of patients with type 2 diabetes: Those with obesity and those in whom hypoglycemia is a clinical concern.”
However, they noted that more evidence is needed on the effectiveness of these treatments. "Despite advances in antihypoglycemic therapy, a drug which would lead to substantial prevention of macrovascular and microvascular complications, decreases mortality and is convenient and affordable, remains the undiscovered Holy Grail of diabetes management.”
The trial was funded by Amylin Pharmaceuticals and Eli Lilly.