By Bruce Sylvester
VIENNA, Austria -- October 2, 2009 -- Switching from exenatide to liraglutide in the treatment of type 2 diabetes improves overall glycaemic control and beta-cell function, and appears to provide other benefits, investigators reported at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD). The switch was also well tolerated.
"In the original 26-week portion of the LEAD [Liraglutide Effect and Action in Diabetes]-6 trial, liraglutide showed superior glucose-lowering ability compared with exenatide," said lead investigator John Buse, MD, PhD, Diabetes Care Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, speaking here at oral presentation on September 30. "In this 14-week extension study, we found that switching prior exenatide subjects to liraglutide further improved their Hb A1C [glycosylated haemoglobin] from the end of the first 26 weeks," he added.
The extension study compared switching from exenatide to liraglutide treatment versus continuing liraglutide treatment.
A total of 389 of the subjects who completed LEAD-6 entered the 14-week nonrandomised extension phase, and 386 completed the extension.
Subjects were either switched from exenatide 10 mcg twice daily to liraglutide 1.8 mg once daily (n = 186 evaluable at endpoint) following a 2-week lead-in of 0.6 mg once daily for 1 week and 1.2 mg once daily for 1 week, or they continued on liraglutide 1.8 mg once daily (n = 200 evaluable at endpoint).
Subjects switching from exenatide to liraglutide achieved further improvements in glycaemic control from week 26 with Hb A1C decreasing by 0.32% (P < .0001), 57% of switched subjects reaching Hb A1C target <7.0% by week 40, and fasting plasma glucose significantly falling by 0.9 mmol/L (P < .0001).
Significant improvements in beta-cell function were also reported, with homeostasis model assessment index of beta-cell function levels increasing by 14.5% (P <= .001).
Statistically significant additional reductions were seen in body weight and systolic blood pressure for the exenatide-to-liraglutide group (P < .001), as well as for the liraglutide-to-liraglutide group (P < .05).
Also, switching from exenatide to liraglutide produced a decreased rate of minor hypoglycaemia (2.6 vs 1.3 events/patient/year for weeks 0 to 26 and weeks 26 to 40, respectively). Continuing liraglutide subjects reported 0.7 events/patient/year during the extension phase (vs 1.9 events/patient/year from weeks 0 to 26).
Lower rates of nausea were reported during the extension study compared with the main trial. The proportion of subjects reporting nausea fell from 28% and 25.5% for the exenatide-to-liraglutide group and the liraglutide-to-liraglutide group, respectively, during the main trial to 3.2% and 1.5%, respectively, during the extension. No pancreatitis was reported.
"Switching from exenatide to liraglutide is well tolerated, and provides additional benefits in overall glycaemic control and beta-cell function while also reducing body weight and systolic blood pressure," the authors concluded. "Maintaining liraglutide treatment achieves durable glycaemic control, weight loss and systolic blood pressure reductions with minimal levels of hypoglycaemia and nausea."
Funding for this study was provided by Novo Nordisk A/S.
[Presentation title: A Switch From Twice-Daily Exenatide to Once-Daily Liraglutide Further Improves Glycaemic Control in Patients With Type 2 Diabetes on Oral Agents. Abstract 2]
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