Although 10 different classes of drug that reduce blood glucose levels are available, treatment of type 2 diabetes may still be unsatisfactory, and the development of new drugs might help. Glucagon-like peptide-1 (GLP-1), secreted by intestinal cells, stimulates insulin secretion and inhibits glucagon secretion in response to blood glucose levels. It also diminishes appetite and promotes proliferation of pancreatic beta cells. GLP-1 itself is rapidly degraded by dipeptidyl peptidase-4, but two types of drug have been developed; GLP-1 receptor agonists and human GLP-1 analogues resistant to the enzyme. Now liraglutide (an enzyme-resistant analogue of GLP-1) and exenatide (a GLP-1 receptor agonist) have been compared in a multinational trial.
A total of 264 adults with poorly controlled type 2 diabetes on maximum tolerated doses of metformin, a sulphonylurea or both were randomized to subcutaneous liraglutide 1.8 mg once daily or subcutaneous exenatide 10 µg twice daily for 26 weeks. Liraglutide caused significantly greater reductions in HbA1c than did exenatide (from an overall mean baseline level of 8.2%, a mean reduction of 1.12% with liraglutide and 0.79% with exenatide). An HbA1c level of <7% was achieved by 54% versus 43%. The reduction in mean fasting plasma glucose was 1.61 versus 0.6 mmol/L. Weight loss was 3.24 kg versus 2.87 kg. Nausea and minor hypoglycaemia were both less frequent with liraglutide. Major hypoglycaemia occurred in two patients on a combination of exenatide and a sulphonylurea.
The results were better with liraglutide. Liraglutide might be suitable treatment when weight gain and hypoglycaemia are problems.
Buse JB, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47; De Block CEM, Van Gaal LF. GLP-1 receptor agonists for type 2 diabetes.