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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Show detailsOVERVIEW
Introduction
Lixisenatide is a recombinant DNA produced polypeptide analogue of human glucagon-like peptide-1 (GLP-1) which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other antidiabetic agents. Therapy with lixisenatide has not been associated with serum enzyme elevations or with episodes of clinically apparent liver injury.
Background
Lixisenatide (lix" i sen' a tide) is a glucagon-like peptide-1 (GLP-1) analogue (also called a GLP-1 receptor agonist) that acts like the native gastrointestinal hormone (incretin) to increase insulin secretion. Lixisenatide, like other GLP-1 analogues, also suppress glucagon production and slows gastric emptying, features that may increase the beneficial effects in type 2 diabetes. Lixisenatide is a recombinant DNA-produced polypeptide that is 44 amino acids in length with a single proline substitution and a modified C-terminus of six lysine molecules that makes it relatively resistant to degradation by dipeptidyl peptidase 4 (DPP4) and extends its half-life allowing for once daily dosing. In multiple preregistration clinical trials, lixisenatide was shown to improve glycemic control and lower HbA1c levels in patients with inadequately controlled type 2 diabetes. Lixisenatide was approved in the United States in 2016 and current indications are for management of glycemic control in adults with type 2 diabetes in combination with diet and exercise, with or without other oral hypoglycemic agents or insulin. Lixisenatide is available under the brand name Adlyxin in multiuse prefilled pens (50 and 100 µg/mL). The recommended starting dose is 10 µg once daily which after 2 weeks can be increased to 20 µg once daily. A fixed combination of lixisenatide (33 µg/mL) with insulin glargine (100 units/mL) is also available under the brand name Soliqua (100/33). Lixisenatide is generally well tolerated, but side effects can be dose limiting and include injection site reactions, diarrhea, nausea, vomiting, dizziness, headache, fatigue and hypoglycemia. Rare adverse events include pancreatitis, severe hypoglycemia, acute renal injury and hypersensitivity reactions.
Hepatotoxicity
In large clinical trials, serum enzyme elevations were no more common with lixisenatide therapy than with placebo or comparator agents. In pooled safety analyses of more than 5000 patients, ALT elevations above 3 times the upper limit of normal occurred in 0.6% of both lixisenatide and placebo groups and no instances of treatment related clinically apparent liver injury were reported. Since licensure, there have been no published case reports of hepatotoxicity due to lixisenatide and the product label does not list liver injury as an adverse event. Thus, liver injury due to lixisenatide, as with other GLP-1 analogues, must be rare, if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
Lixisenatide is a polypeptide and is metabolized to amino acids by serum and tissue proteases, and is unlikely to have any direct hepatotoxic potential. Lixisenatide acts through the incretin pathway to affect glucose metabolism and, thus, is often grouped with other incretin based antidiabetic mediations such as the DPP-4 inhibitors, sitagliptin, saxagliptin and linagliptin, and other GLP-1 analogues such as exenatide, liraglutide, dulaglutide and albiglutide which are also discussed in LiverTox.
References regarding the hepatotoxicity and safety of lixisenatide are given with the Overview section of the GLP-1 Analogues.
Drug Class: Antidiabetic Agents
Other Drugs in the Subclass, Incretin-Based Drugs, Glucagon-Like Peptide-1 (GLP-1) Analogues: Albiglutide, Dulaglutide, Exenatide, Liraglutide, Semaglutide
PRODUCT INFORMATION
REPRESENTATIVE TRADE NAMES
Lixisenatide – Adlyxin®
DRUG CLASS
Antidiabetic Agents
Product labeling at DailyMed, National Library of Medicine, NIH
CHEMICAL FORMULA AND STRUCTURE
DRUG | CAS REGISTRY NUMBER | MOLECULAR FORMULA | STRUCTURE |
---|---|---|---|
Lixisenatide | 320367-13-3 | Protein | Complex Polypeptide |
- PubChem SubstanceRelated PubChem Substances
- Review The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus.[Expert Opin Drug Discov. 2014]Review The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus.Christensen M, Miossec P, Larsen BD, Werner U, Knop FK. Expert Opin Drug Discov. 2014 Oct; 9(10):1223-51. Epub 2014 Aug 14.
- Review Glucagon-Like Peptide-1 (GLP-1) Analogues.[LiverTox: Clinical and Researc...]Review Glucagon-Like Peptide-1 (GLP-1) Analogues.. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012
- Review Lixisenatide, a Once-Daily Prandial Glucagon-Like Peptide-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes.[Pharmacotherapy. 2017]Review Lixisenatide, a Once-Daily Prandial Glucagon-Like Peptide-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes.Trujillo JM, Goldman J. Pharmacotherapy. 2017 Aug; 37(8):927-943. Epub 2017 Jul 26.
- Review Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis.[Diabetes Obes Metab. 2017]Review Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis.Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Diabetes Obes Metab. 2017 Apr; 19(4):524-536. Epub 2017 Feb 17.
- Review Lixisenatide, a novel GLP-1 receptor agonist: efficacy, safety and clinical implications for type 2 diabetes mellitus.[Diabetes Obes Metab. 2014]Review Lixisenatide, a novel GLP-1 receptor agonist: efficacy, safety and clinical implications for type 2 diabetes mellitus.Bolli GB, Owens DR. Diabetes Obes Metab. 2014 Jul; 16(7):588-601. Epub 2014 Jan 20.
- Lixisenatide - LiverToxLixisenatide - LiverTox
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