The European Commission has granted marketing authorization to Byetta (exenatide twice-daily) as an adjunctive therapy to basal insulin, with or without metformin and/or Actos® (pioglitazone), for the treatment of type 2 diabetes in adults who have not achieved adequate glycemic control with these agents.
The EU approval was given after a clinical trial of patients using fixed-dose Byetta with titrated basal insulin. The patients in the trial achieved better postprandial and overall glycemic control, without weight gain or an increased risk of hypoglycemia, compared to patients using titrated basal insulin without Byetta .
The study included in the EU marketing authorization submission package was a double-blind, 30-week clinical trial published in Annals of Internal Medicine. In the study, Byetta 10 micrograms or placebo was added to existing insulin glargine (Lantus) therapy (with or without metformin, pioglitazone or both), which was titrated to achieve target fasting glucose levels. At study entry, patients who may have been at increased risk of hypoglycemia (A1c less than or equal to 8 percent) reduced their dose of Lantus by 20 percent. Five weeks after randomization, all patients had insulin doses titrated to achieve target fasting glucose levels. The primary endpoint was reduction in A1c, a measure of average blood sugar over three months; secondary endpoints included change in body weight along with other parameters of glucose control, cardiovascular health, hypoglycemia and patient-reported outcomes.
After 30 weeks of treatment, Byetta demonstrated a statistically significant reduction in A1c compared to placebo, lowering A1c by 1.7 percentage points from a baseline of 8.3 percent. Patients treated with optimized insulin glargine plus placebo experienced a 1.0 percentage point decrease in A1c from a baseline of 8.5 percent. Patients who added Byetta to their insulin glargine regimen saw their weight decrease by an average of 4 pounds, compared with an increase of 2 pounds in patients who were treated with optimized insulin glargine plus placebo. Byetta is not indicated for the management of obesity and weight loss was a secondary endpoint in the trial. Change in fasting glucose and hypoglycemia incidence were similar between treatment groups.