Investigational Drug Details
| Drug ID: | D205 |
| Drug Name: | Linagliptin |
| Synonyms: | (R)-8-(3-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methylquinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione; Linagliptin |
| Type: | Chemical drug |
| DrugBank ID: | DB08882 |
| DrugBank Description: | Linagliptin is a DPP-4 inhibitor developed by Boehringer Ingelheim for the treatment of type II diabetes . Linagliptin differs from other DPP-4 inhibitors in that it has a non-linear pharmacokinetic profile, is not primarily eliminated by the renal system, and obeys concentration dependant protein binding. Linagliptin was approved by the FDA on May 2, 2011. |
| PubChem ID: | 10096344 |
| CasNo: | 668270-12-0 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(C#CC)n1c2c(nc1N1C[C@H](N)CCC1)n(C)c(=O)n(c2=O)Cc1nc2c(c(n1)C)cccc2 |
| Structure: |
|
| InChiKey: | LTXREWYXXSTFRX-QGZVFWFLSA-N |
| Molecular Weight: | 472.553 |
| DrugBank Targets: | Dipeptidyl peptidase 4 inhibitor |
| DrugBank MoA: | Linagliptin is a competitive, reversible DPP-4 inhibitor. Inhibition of this enzyme slows the breakdown of GLP-1 and glucose-dependant insulinotropic polypeptide (GIP). GLP-1 and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic beta cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose. |
| DrugBank Pharmacology: | A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose. |
| DrugBank Indication: | Linagliptin is indicated for the treatment of type II diabetes in addition to diet and exercise. It should not be used to treat type I diabetes or in diabetic ketoacidosis. An extended-release combination product containing empagliflozin, linagliptin, and metformin was approved by the FDA in January 2020 for the improvement of glycemic control in adults with type 2 diabetes mellitus when used adjunctively with diet and exercise. |
| Targets: | DPP4 inhibitor |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Clinical trial on-going (JPRN-UMIN000014864) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0374 | IRCT20210922052550N1 | Phase 3 | Recruiting | No Results Available | 07/11/2021 | 7 February 2022 | Details |
| L0896 | JPRN-UMIN000014864 | Not selected | Not Recruiting | No Results Available | 15/08/2014 | 2 April 2019 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A05485 | 33236464 | Diabetes Obes Metab | Metformin dose increase versus added linagliptin in non-alcoholic fatty liver disease and type 2 diabetes: An analysis of the J-LINK study. | Details |
| A05828 | 33105604 | Int J Mol Sci | Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor. | Details |
| A06587 | 32819262 | Curr Drug Saf | Efficacy and Cardiovascular Safety of DPP-4 Inhibitors. | Details |
| A08062 | 32259637 | Mol Cell Endocrinol | Anti-steatotic linagliptin pleiotropic effects encompasses suppression of de novo lipogenesis and ER stress in high-fat-fed mice. | Details |
| A10685 | 31236880 | Bull Exp Biol Med | Effect of Linagliptin on the Ratio of Apoptosis Regulators in the Model of Non-Alcoholic Fatty Liver Disease in db/db Mice. | Details |
| A13463 | 29959534 | Med Mol Morphol | Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes. | Details |
| A14854 | 29203247 | Biochem Biophys Res Commun | Co-administration of APD668, a G protein-coupled receptor 119 agonist and linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in mice fed on a high trans-fat diet. | Details |
| A15966 | 28635324 | Antioxid Redox Signal | Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nonalcoholic Steatohepatitis and Liver Fibrosis. | Details |
| A16632 | 28274625 | Eur J Pharmacol | APD668, a G protein-coupled receptor 119 agonist improves fat tolerance and attenuates fatty liver in high-trans fat diet induced steatohepatitis model in C57BL/6 mice. | Details |
| A17234 | 27895822 | World J Diabetes | Linagliptin alleviates fatty liver disease in diabetic db/db mice. | Details |
| A17943 | 27462372 | Diabetol Metab Syndr | Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. | Details |
| A23089 | 24048504 | Med Mol Morphol | Linagliptin alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis. | Details |
| A23630 | 23613622 | World J Gastroenterol | Dipeptidyl peptidase-4: a key player in chronic liver disease. | Details |
| A49802 | 35633911 | World J Gastroenterol | Peroxisome proliferator-activated receptor-alpha activation and dipeptidyl peptidase-4 inhibition target dysbiosis to treat fatty liver in obese mice. | Details |
| A50713 | 35290413 | PLoS One | Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4-With improving insulin resistance. | Details |
| A52017 | 32282852 | PLoS One | Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data. | Details |