Early clinical studies with liraglutide.
OBJECTIVE
To describe Phase 1 and 2 clinical trials of liraglutide with a focus on clinical pharmacology.


RESULTS
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 (HbA(1c) ) 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 HbA(1c) < 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.
Schmidt
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Dept of Medicine I, St. Josef Hospital, Ruhr-University of Bochum Medical School, Bochum, Germany. Wolfgang.e.schmidt@ruhr-unibochum.de
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents; D002318:Cardiovascular Diseases / Q000150:complications; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019468:Disease Management; D004359:Drug Therapy, Combination; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects; D000069450:Liraglutide; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D001786:Blood Glucose; D002316:Cardiotonic Agents; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D008687:Metformin