Investigational Drug Details
| Drug ID: | D383 |
| Drug Name: | Vildagliptin |
| Synonyms: | Vitagliptin; Galvus; Jalra; Xiliarx |
| Type: | Chemical drug |
| DrugBank ID: | DB04876 |
| DrugBank Description: | Vildagliptin (LAF237) is an orally active antihyperglycemic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme. It is used to manage type II diabetes mellitus, where GLP-1 secretion and insulinotropic effects are impaired. By inhibiting DPP-4, vildagliptin prevents the degradation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are incretin hormones that promote insulin secretion and regulate blood glucose levels. Elevated levels of GLP-1 and GIP consequently results in improved glycemic control. In clinical trials, vildagliptin has a relatively low risk of hypoglycemia. Oral vildagliptin was approved by the European Medicines Agency in 2008 for the treatment of type II diabetes mellitus in adults as monotherapy or in combination with , a sulfonylurea, or a thiazolidinedione in patients with inadequate glycemic control following monotherapy. It is marketed as Galvus. Vildagliptin is also available as Eucreas, a fixed-dose formulation with metformin for adults in who do not adequately glycemic control from monotherapy. Vildagliptin is currently under investigation in the US. |
| PubChem ID: | 6918537 |
| CasNo: | 274901-16-5 |
| Repositioning for NAFLD: | Yes |
| SMILES: | N(CC(=O)N1[C@H](C#N)CCC1)C12CC3(O)CC(C2)CC(C1)C3 |
| Structure: |
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| InChiKey: | SYOKIDBDQMKNDQ-XWTIBIIYSA-N |
| Molecular Weight: | 303.406 |
| DrugBank Targets: | Dipeptidyl peptidase 4 inhibitor |
| DrugBank MoA: | Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones that regulate blood glucose levels and maintain glucose homeostasis. It is estimated that the activity of GLP-1 and GIP contribute more than 70% to the insulin response to an oral glucose challenge. They stimulate insulin secretion in a glucose-dependent manner via G-protein-coupled GIP and GLP-1 receptor signalling. In addition to their effects on insulin secretion, GLP-1 is also involved in promoting islet neogenesis and differentiation, as well as attenuating pancreatic beta-cell apoptosis. Incretin hormones also exert extra-pancreatic effects, such as lipogenesis and myocardial function. In type II diabetes mellitus, GLP-1 secretion is impaired, and the insulinotropic effect of GIP is significantly diminished. Vildagliptin exerts its blood glucose-lowering effects by selectively inhibiting dipeptidyl peptidase-4 (DPP-4), an enzyme that rapidly truncates and inactivates GLP-1 and GIP upon their release from the intestinal cells. DPP-4 cleaves oligopeptides after the second amino acid from the N-terminal end. Inhibition of DPP-4 substantially prolongs the half-life of GLP-1 and GIP, increasing the levels of active circulating incretin hormones. The duration of DPP-4 inhibition by vildagliptin is dose-dependent. Vildagliptin reduces fasting and prandial glucose and HbA1c. It enhances the glucose sensitivity of alpha- and beta-cells and augments glucose-dependent insulin secretion. Fasting and postprandial glucose levels are decreased, and postprandial lipid and lipoprotein metabolism are also improved. |
| DrugBank Pharmacology: | Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control. In clinical trials, treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta-cells, proinsulin to insulin ratio, and measures of beta-cell responsiveness from the frequently-sampled meal tolerance test. Vildagliptin has improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels. |
| DrugBank Indication: | Vildagliptin is indicated in the treatment of type II diabetes mellitus in adults. As monotherapy, vildagliptin is indicated in adults inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance. It is also indicated as dual therapy in combination with metformin, a sulphonylurea, or a thiazolidinedione in adults patients with insufficient glycemic control despite maximal tolerated dose of monotherapy. Vildagliptin is also marketed in a combination product with for the treatment of adults with type II diabetes mellitus who inadequately respond to either monotherapy of vildagliptin or metformin. This fixed-dose formulation can be used in combination with a sulphonylurea or insulin (i.e., triple therapy) as an adjunct to diet and exercise in adults who do not achieve adequate glycemic control with monotherapy or dual therapy. |
| Targets: | DPP4 inhibitor |
| Therapeutic Category: | Antidiabetic drug |
| Clinical Trial Progress: | Phase 3 on-going (NCT03925701) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0751 | NCT03925701 | Phase 3 | Recruiting | No Results Available | 22/04/2019 | 12 December 2020 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A06587 | 32819262 | Curr Drug Saf | Efficacy and Cardiovascular Safety of DPP-4 Inhibitors. | Details |
| A12334 | 30510994 | Cell Mol Gastroenterol Hepatol | Dipeptidyl Peptidase 4 Inhibitors Reduce Hepatocellular Carcinoma by Activating Lymphocyte Chemotaxis in Mice. | Details |
| A12660 | 30341231 | Postgrad Med J | Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis. | Details |
| A16938 | 28083033 | Pak J Med Sci | Vildagliptin ameliorates biochemical, metabolic and fatty changes associated with non alcoholic fatty liver disease. | Details |
| A22461 | 24550584 | Indian J Pharmacol | Combination of vildagliptin and rosiglitazone ameliorates nonalcoholic fatty liver disease in C57BL/6 mice. | Details |
| A23630 | 23613622 | World J Gastroenterol | Dipeptidyl peptidase-4: a key player in chronic liver disease. | Details |
| A44112 | 29721506 | Biomed Res Int | Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet. | Details |
| A44437 | 28631945 | Curr Med Res Opin | Vildagliptin: any effect on non-alcoholic fatty liver disease and serum uric acid? Re: Shelbaya S, Rakha S. Effectiveness and safety of vildagliptin and vildagliptin add-on to metformin in real-world settings in Egypt - results from the GUARD study. Curr Med Res Opin 2017;33:797-801. | Details |
| A49685 | 35671811 | Life Sci | Vildagliptin alleviates liver fibrosis in NASH diabetic rats via modulation of insulin resistance, oxidative stress, and inflammatory cascades. | Details |
| A52855 | 20625970 | Horm Metab Res | Combination therapy with nateglinide and vildagliptin improves postprandial metabolic derangements in Zucker fatty rats. | Details |