The U.S. Food and Drug administration has approved a new indication for fixed-dose exenatide injections.
The medication’s manufacturers, Amylin and Eli Lilly, announced Oct. 19 that the exenatide injections, marketed as Byetta, had been approved as an add-on therapy to insulin glargine, with or without metformin and/or a thiazolidinedione, for adults with type 2 diabetes who are not achieving adequate glycemic control on long-acting insulin alone.
Exenatide was initially approved by the FDA in 2005 for use in combination with metformin with or without a sulfonylurea, and later for use with thiazolidinediones (TZDs). The medicine is modeled on a protein found in the saliva of Gila monsters, and is similar to glucose-dependent insulinotropic peptide or GLP-1, but lasts longer in the body.
In a phase III, manufacturer-sponsored, randomized, controlled trial of exenatide injections (Ann. Intern. Med. 2011;154:103-12), the findings of which were submitted to the FDA in support of the new indication, 261 patients receiving insulin glargine, with or without metformin and/or a TZD were randomized to receive exenatide 10 mcg twice daily or placebo in addition to aggressive insulin titration for 30 weeks.
Hemoglobin A1c was seen to decrease by 1.74 percentage points after 30 weeks in patients in the exenatide arm, and by 1.04 points in those treated with insulin alone. Patients receiving exenatide required less insulin (increases in insulin dosage of 13 U/day for the treatment arm vs. 20 U/day in the control arm). The incidence of hypoglycemia was similar between arms.
Patients’ weights in the exenatide arm of the study also decreased by 1.8 kg, compared with an increase of 1 kg in the control arm, suggesting that exenatide improved glycemic control without causing weight gain. Nausea was the most frequently reported adverse event, affecting 41% in the treatment arm and 8% in the control arm.
Letters criticizing the study appeared after its publication. One questioned whether it was adequately powered to detect some of the reported effects, and another took issue with its short duration and use of HbA1c as an outcome measure, when other, longer studies had not shown correlations between improvements in HbA1c and diabetes mortality or vascular complications.