Safety and tolerability of glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes

Abstract

Conventional pharmacotherapies for type 2 diabetes effectively lower blood glucose levels but are associated with side effects that preclude their optimal use or raise safety concerns. Novel treatments based on the endogenous hormone glucagon-like peptide-1 (GLP-1) may overcome some of these obstacles. The GLP-1 receptor agonists, exenatide and liraglutide, have a lower risk of hypoglycaemia than some conventional agents and can provide significant weight loss. Although they can cause gastrointestinal symptoms, effects are transient and can be reduced by gradual dose escalation. No cardiac safety issues have been reported and animal studies suggest that they may confer cardiovascular benefits. Pancreatitis has occurred among patients receiving GLP-1 receptor agonists, but it is unclear whether this is drug-related or due to the increased risk of pancreatitis in type 2 diabetes. Despite findings in rodents that GLP-1 receptor activation of thyroid C-cells results in calcitonin release and C-cell pathology, such effects have not been seen with long-term exposure in humans. Immunogenicity does not appear to be a safety concern. In summary, currently available data indicate that GLP-1 receptor agonists provide an effective and generally well tolerated therapeutic option for the management of type 2 diabetes.