Aims: To describe Phase 1 and 2 clinical trials of liraglutide with a focus on clinical pharmacology.
Key findings: In early clinical trials of liraglutide, 0.05–1.9 mg daily improved multiple aspects of glycaemic control and beta-cell function. Early trials demonstrated typical reductions in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) of up to 1.5% and 3.3–3.9 mmol/l, respectively, at daily doses of 1.25–1.9 mg, with 45–50% of patients reaching HbA1c < 7%. The effects of liraglutide in restoring beta-cell response to fasting and postprandial hyperglycaemia and in reinstating near-normal insulin secretion under hyperglycaemic conditions suggest a beta-cell-protective effect. By delaying gastric emptying and promoting satiety, liraglutide is weight sparing at low doses and causes clinically meaningful weight loss at higher doses and in combination with other anti-diabetes therapies with weight-modifying benefits, such as metformin. Significant improvements in other cardiovascular risk factors, including blood pressure, lipids and cardiovascular risk biomarkers, were also evident. Adverse effects of liraglutide were primarily gastrointestinal; dose-dependent nausea was the most commonly reported effect, but was typically mild-to-moderate in severity and transient in nature.
Conclusions: Early clinical trials of liraglutide indicate the ability to improve glycaemic control in a glucose-dependent manner, with low risk of hypoglycaemia. Promotion of weight loss, along with improvements in multiple cardiovascular risk factors, suggests that liraglutide may offer a novel and clinically valuable approach to disease management for patients with type 2 diabetes.