New treatments in type 2 diabetes: a focus on the incretin-based therapies.
The demonstration that the incretin hormone glucagon-like peptide 1 can improve glycaemic control in patients with type 2 diabetes has led to the rapid development during the last decade of promising new classes of agent for the management of type 2 diabetes. These agents possess a range of physiological effects that are associated with improved glycaemic control in diabetes including stimulation of glucose-dependent insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, and reduction of food intake. In addition, preclinical studies suggest that incretin-based therapies may improve beta-cell function via enhancement of beta-cell mass and induction of genes important for differentiated beta-cell function. Exenatide, and the dipeptidyl peptidase-4 inhibitors, sitagliptin and vildagliptin are already approved, and liraglutide is currently completing Phase 3 trials. As these agents and standard oral therapies for type 2 diabetes lower glucose levels through different, but potentially complementary mechanisms, their use in combination should provide effective, potentially additive, glycaemic control. The incretin-based therapies also offer other advantages such as weight loss with exenatide and liraglutide, a reduced risk of hypoglycaemia, and as suggested by preclinical studies, a potential beta-cell preserving effect. Long-term outcome and safety data are not available for these agents, but they appear generally well-tolerated in comparison with existing therapies for type 2 diabetes. The multiple underlying glucose-lowering actions of the incretin-based therapies, as well as a lack of weight gain or even weight loss, make these important new additions to available antidiabetic agents expanding the treatment options available for patients.
Barnett
Anthony H
AH
University of Birmingham and Heart of England National Health Service Foundation Trust (Teaching), Birmingham, UK. anthony.barnett@heartofengland.nhs.uk
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology / Q000517:prevention & control; D054795:Incretins / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D012307:Risk Factors; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D054795:Incretins; D007328:Insulin