Liraglutide: clinical pharmacology and considerations for therapy
Abstract
Liraglutide is a United States Food and Drug Administration (FDA)‐approved glucagon‐like peptide−1 (GLP‐1) analog that is 97% homologous to native human GLP‐1. The additional 16‐carbon fatty acid chain causes noncovalent binding to albumin, which slows absorption from the injection site and protects the molecule from degradation by the enzyme dipeptidyl peptidase‐4, allowing for protraction of action. Albumin binding and an elimination half‐life of 13 hours combine to allow for once‐daily dosing. Liraglutide 1.2 and 1.8 mg/day given as monotherapy for up to 52 weeks produced mean reductions in hemoglobin A 1c (A1C) of 0.6–1.6%; combination therapy of liraglutide with oral antidiabetic agents demonstrated mean A1C reductions up to 1.5%. The satiety effect of GLP‐1 receptor agonists and documented weight loss as great as 3.38 kg in clinical trials may make liraglutide ideal for obese patients with type 2 diabetes mellitus. Like other incretin‐based agents, preliminary studies suggest liraglutide may also increase β‐cell mass and function. Hypoglycemia is rare with liraglutide and tends to occur when used in combination with sulfonylureas; liraglutide in combination with insulin is not yet FDA approved. The pharmacokinetic parameters of liraglutide are unaffected by age, sex, race, or ethnicity, and no special recommendations for altered dosing of liraglutide need apply to populations with hepatic or renal impairment. Results from clinical trials have not shown an increased risk of medullary thyroid cancer, pancreatitis, or poor cardiovascular outcomes with liraglutide treatment. Ongoing, long‐term monitoring studies continue to evaluate the safety of liraglutide treatment in these outcomes.
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Semaglutide has an extended half-life of 1 week compared to liraglutide (~13 h).
“This risk appears most prominent with semaglutide, given its extended half-life of 1 week,38 compared to liraglutide (∼13 h).39”
From Metabolic rebound after GLP-1 receptor agonist discontinuation: a systematic review and meta-analysis (2025) · cites this paper as [39]
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- Authors
- Sisson, E. M.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Sisson, Evan M.
- ORCID
- Sisson, Evan M.
- Venue
- Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Publisher
- Wiley
- Published
- 2011-09
- Volume
- 31
- Issue
- 9
- Pages
- 896-911
- ISSN
- 0277-0008 (ISSN-L)
- 1875-9114
- OpenAlex
- W2085142826
- Cited by
- 49
- References
- 70
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 8 · 2023: 5 · 2022: 1 · 2021: 2 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- liraglutide, GLP-1 receptor agonists, type 2 diabetes, obesity, albumin binding, dipeptidyl peptidase IV, pharmacokinetics, weight loss, beta-cell function, hypoglycemia, medullary thyroid carcinoma, pancreatitis, cardiovascular outcomes, renal and hepatic impairment, sulfonylureas, insulin combination therapy
- MeSH terms
- Liraglutide, Humans, Hypoglycemic Agents, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors
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