In a month-long head-to-head trial, the incretin mimetic exenatide (Byetta) reduced postprandial glucose in type 2 diabetes more than did sitagliptin (Januvia), an oral DPP-4 inhibitor, researchers reported. The results of the double-blind crossover study suggested that direct reproduction of GLP-1 with exenatide was more effective than indirect enhancement of GLP-1 via DPP-4 inhibition, said Ralph DeFronzo, M.D., of the University of Texas Health Science Center San Antonio. Dr. DeFronzo was a co-author of the study and chair of the European Association for the Study of Diabetes poster session where the results were reported.
GLP-1-based therapies reproduce or enhance the actions of the naturally occurring peptide, GLP-1, and control glucose without causing weight gain. Sitagliptin is a DPP-4 inhibitor.
The finding was based on an intention-to-treat analysis in 95 patients ages 18 to 70. All patients were on a stable metformin treatment regimen and all had baseline hemoglobin A1c from 7% to 11% and fasting plasma glucose of less than 15.5 mmol/L.
The primary endpoint of the trial was two-hour postprandial glucose and secondary endpoints included postprandial insulin, glucagon, active GLP-1, triglycerides, insulin secretion rate, acetaminophen absorption, exenatide pharmacokinetics, and safety.
After two weeks on sitagliptin or exenatide, patients were crossed over to the other therapy. The researchers had evaluable data on 61 patients.
When patients were treated with exenatide, their postprandial glucose levels averaged 133 mg/dL versus 208 mg/dL when patients were treated with sitagliptin (P<0.0001). Likewise, other parameters including acute insulin response, suppression of glucagon secretion, and postprandial concentration of active GLP-1, all favored exenatide treatment.
But other researchers criticized the endpoint of the trial, postprandial glucose, and the trial’s duration — two weeks before crossing patients over to a different treatment.
Tina Vilsbøll, M.D., of Gentofte Hospital at the University of Copenhagen, stated that, while the trial was interesting, it was "not a true head-to-head comparison because for that you need a trial to last at least 12 weeks and you need a clinically meaningful endpoint — hemoglobin A1c."
She added that it was well known that two-hour postprandial glucose does not decrease with sitagliptin treatment.
Moreover, 34% of exenatide patients versus 12% of sitagliptin patients experienced nausea and 25% of the exenatide patients reported vomiting versus 3% of the sitagliptin patients. "So you have nausea, vomiting, and injections to consider," Dr. Vilsbøll said.
DeFronzo R, et al "Exenatide resulted in significantly greater improvements in postprandial glycaemic control compared to sitagliptin" EASD 2008; Abstract 872.
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