San Diego, CA—The investigational once-weekly form of exenatide (Bydureon) was equally effective to metformin, slightly less effective than pioglitazone, and significantly superior to sitagliptin in achieving glycemic control in drug-naïve patients with type 2 diabetes not adequately controlled with diet and exercise in the 26-week DURATION-4 study.
“All 4 drugs achieved a robust improvement in A1c. Exenatide once-weekly was superior to sitagliptin and noninferior to metformin, but not to pioglitazone. Exenatide may be an alternative option for initial therapy of type 2 diabetes mellitus,” said researcher David Russell-Jones, MD, consultant physician at the Royal Surrey Hospital, and Professor at the University of Surrey, Guldford, UK, who presented the study at the 2011 Scientific Sessions of the American Diabetes Association.
At the end of the study, patients receiving exenatide achieved a mean reduction in hemoglobin (Hb)A1c of –1.5% from baseline versus –1.2% for sitagliptin, –1.5% for metformin, and –1.6% for pioglitazone. The percentage of patients who reached target HbA1c was 63% for exenatide, 55% for metformin, 43% for sitagliptin, and 61% for pioglitazone.
Exenatide achieved similar weight loss to metformin (about 2 kg), whereas the other 2 drugs led to weight gain. Few episodes of hypoglycemia were reported in any arm, and quality of life improved with all 4 treatments.
The researchers enrolled 820 previously untreated patients with an average disease duration of 3 years in the 26-week, double-blind, randomized, 4-arm parallel-group study. Randomization was in a 3:3:2:2 ratio of exenatide once-weekly (n = 248), metformin (n = 246), sitagliptin (n = 163), and pioglitazone (n = 163).
The most common adverse events for exenatide were nausea and diarrhea; for metformin, diarrhea and headache; for sitagliptin, upper respiratory tract infection and headache; and for pioglitazone, upper respiratory tract infection, headache, hypertension, and peripheral edema.
At the presentation, several audience members took issue with Dr Russell-Jones’ conclusion, commenting that if exenatide is noninferior to metformin, metformin would still be the first choice and would be significantly less costly.