Liraglutide in Type 2 Diabetes Mellitus: Clinical Pharmacokinetics and Pharmacodynamics

Abstract

Liraglutide is an acylated glucagon-like peptide-1 analogue with 97 % amino acid homology with native glucagon-like peptide-1 and greatly protracted action. It is widely used for the treatment of type 2 diabetes mellitus, and administered by subcutaneous injection once daily. The pharmacokinetic properties of liraglutide enable 24-h exposure coverage, a requirement for 24-h glycaemic control with once-daily dosing. The mechanism of protraction relates to slowed release from the injection site, and a reduced elimination rate owing to metabolic stabilisation and reduced renal filtration. Drug exposure is largely independent of injection site, as well as age, race and ethnicity. Increasing body weight and male sex are associated with reduced concentrations, but there is substantial overlap between subgroups; therefore, dose escalation should be based on individual treatment outcome. Exposure is reduced with mild, moderate or severe renal or hepatic impairment. There are no clinically relevant changes in overall concentrations of various drugs (e.g. paracetamol, atorvastatin, griseofulvin, digoxin, lisinopril and oral combination contraceptives) when co-administered with liraglutide. Pharmacodynamic studies show multiple beneficial actions with liraglutide, including improved fasting and postprandial glycaemic control (mediated by increased insulin and reduced glucagon levels and minor delays in gastric emptying), reduced appetite and energy intake, and effects on postprandial lipid profiles. The counter-regulatory hormone response to hypoglycaemia is largely unaltered. The effects of liraglutide on insulin and glucagon secretion are glucose dependent, and hence the risk of hypoglycaemia is low. The pharmacokinetic and pharmacodynamic properties of liraglutide make it an important treatment option for many patients with type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0343-6) contains supplementary material, which is available to authorized users.

Postprandial hypoglycaemia after Roux‐en‐Y gastric bypass and the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide

“…This finding was confirmed by CGM, during which treatment with liraglutide increased the lowest IG level, and diminished glycaemic variability and time in hyperglycaemia, while time in hypoglycaemia remained unchanged. It is possible that the effects observed in the present CGM data and in previous reports could be explained by treatment‐induced changes in food intake and appetite and/or by a slowing of the intestinal transit time . In contrast, deceleration of gastric emptying seems less likely, given the rapid pouch‐emptying seen after RYGB .…”

Glucagon‐like peptide‐1 receptor agonists in type 2 diabetes treatment: are they all the same?

“…As a result, peak‐to‐trough fluctuations are more pronounced with short‐acting agents than with long‐acting agents . Steady‐state plasma concentrations of the long‐acting agents are reached from between ~3 days (liraglutide) to 6 to 7 weeks (exenatide once weekly), with albiglutide, dulaglutide, and semaglutide having intermediate values…”

Liraglutide (Saxenda<sup>®</sup>) as a Treatment for Obesity

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