Investigational Drug Details
| Drug ID: | D129 |
| Drug Name: | Exenatide |
| Synonyms: | Exenatide; Exenatide synthetic; Exendin 4; Exendin-4; Synthetic exendin-4 |
| Type: | Biological drug |
| DrugBank ID: | DB01276 |
| DrugBank Description: | Exenatide is a glucagon-like peptide-1 (GLP-1) analog. It functions to activate the GLP-1 receptor and increases insulin secretion, decrease glucagon secretion, and slow gastric emptying to improve glycemic control. Exenatide was given FDA approval on April 28, 2005. |
| PubChem ID: | 45588096 |
| CasNo: | 141758-74-9 |
| Repositioning for NAFLD: | Yes |
| SMILES: | S(CC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](N)Cc1nc[nH]c1)CCC(=O)O)[C@H](O)C)Cc1ccccc1)[C@H](O)C)CO)CC(=O)O)CC(C)C)CO)CCCCN)CCC(=O)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H]([C@H](CC)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N1[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N2[C@H](C(=O)N3[C@@H](CCC3)C(=O)N3[C@@H](CCC3)C(=O)N[C@@H](CO)C(=O)N)CCC2)C)CO)CO)CCC1)CC(=O)N)CCCCN)CC(C)C)Cc1c2c([nH]c1)cccc2)CCC(=O)O)Cc1ccccc1)C)CCC(=O)O)CCC(=O)O)CCC(=O)O)C |
| Structure: |
|
| InChiKey: | HTQBXNHDCUEHJF-XWLPCZSASA-N |
| Molecular Weight: | 4186.637 |
| DrugBank Targets: | Glucagon-like peptide 1 receptor agonist |
| DrugBank MoA: | Exenatide is a human glucacon-like peptide-1(GLP-1) receptor agonist. By activating this receptor, insulin secretion is increased and glucagon secretion is decreased in a glucose dependant manner. Exenatide also slows gastric emptying and decreases food intake. These effects work synergistically to improve glycemic control by reducing the likelihood of hyper and hypoglycemia. |
| DrugBank Pharmacology: | When patients take exenatide the body's natural response to glucose is modulated. More insulin and less glucagon are released in response to glucose, though in cases of hypoglycemia a normal amount of glucagon is released. Exenatide also slows gastric emptying, leading to a slower and prolonged release of glucose into the systemic circulation. Together these effects prevent hyper and hypoglycemia. |
| DrugBank Indication: | Exenatide is indicated for improving glycemic control in adults with type 2 diabetes mellitus along with diet and exercise. |
| Targets: | GLP1R activator; GLP1R agonist |
| Therapeutic Category: | Improve insulin resistance |
| Clinical Trial Progress: | Phase 4 completed (NCT02303730: All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. β-cell function improved in all treatment groups; hence, early initiation of β-cell-protective therapy may halt the decline in β-cell function in type 2 diabetes.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0061 | NCT01006889 | Phase 4 | Completed | Has Results | January 2008 | September 28, 2016 | Details |
| L0070 | NCT02303730 | Phase 4 | Completed | No Results Available | March 2015 | August 28, 2019 | Details |
| L0078 | NCT01208649 | Phase 4 | Completed | No Results Available | July 2008 | September 24, 2010 | Details |
| L0098 | NCT00650546 | Phase 2/Phase 3 | Completed | Has Results | August 2006 | April 11, 2017 | Details |
| L0174 | NCT00529204 | Phase 2 | Terminated | Has Results | October 2007 | June 20, 2017 | Details |
| L0612 | ChiCTR-IPC-15006339 | Post-market | Not Recruiting | No Results Available | 27/04/2015 | 18 April 2017 | Details |
| L0679 | EUCTR2008-002325-37-DE | Not applicable | Authorised | No Results Available | 04/08/2009 | 19 March 2012 | Details |
| L0682 | ISRCTN81902209 | Not applicable | Not Recruiting | Has Results | 13/05/2009 | 13 May 2019 | Details |
| L0683 | EUCTR2008-006928-55-GB | Not applicable | Not Recruiting | No Results Available | 15/04/2009 | 19 March 2012 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00318 | 35140289 | Sci Rep | Exendin-4 alleviates steatosis in an in vitro cell model by lowering FABP1 and FOXA1 expression via the Wnt/-catenin signaling pathway. | Details |
| A00459 | 35072848 | Inflammopharmacology | The effects of metformin, pioglitazone, exenatide and exercise on fatty liver in obese diabetic rats: the role of IRS-1 and SOCS-3 molecules. | Details |
| A00653 | 35014145 | Diabetes Obes Metab | Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: The efficacy and durability of initial combination therapy for type 2 diabetes (EDICT). | Details |
| A00703 | 34997159 | Sci Rep | Evaluation of NAFLD fibrosis, FIB-4 and APRI score in diabetic patients receiving exenatide treatment for non-alcoholic fatty liver disease. | Details |
| A02615 | 34308859 | Nan Fang Yi Ke Da Xue Xue Bao | [Exendin-4 promotes autophagy to relieve lipid deposition in a NAFLD cell model by activating AKT/mTOR signaling pathway]. | Details |
| A03013 | 34164242 | Cureus | Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Non-Alcoholic Steatohepatitis: A Clinical Review Article. | Details |
| A03163 | 34106786 | Am J Physiol Cell Physiol | Impaired Ca2+ signaling due to hepatic steatosis mediates hepatic insulin resistance in Alström syndrome mice that is reversed by GLP-1 analog treatment. | Details |
| A03232 | 34078383 | J Transl Med | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4. | Details |
| A03561 | 33953700 | Front Endocrinol (Lausanne) | Exenatide Attenuates Non-Alcoholic Steatohepatitis by Inhibiting the Pyroptosis Signaling Pathway. | Details |
| A03840 | 33852508 | Eur J Gastroenterol Hepatol | The role of nursing care in the type 2 diabetes treatment associated with chronic liver diseases. | Details |
| A03861 | 33841337 | Front Endocrinol (Lausanne) | Efficacy of Various Hypoglycemic Agents in the Treatment of Patients With Nonalcoholic Liver Disease With or Without Diabetes： A Network Meta-Analysis. | Details |
| A04513 | 33592427 | Clin Res Hepatol Gastroenterol | Integrated expression profiles of mRNA and miRNA in a gerbil model of fatty liver fibrosis treated with exenatide. | Details |
| A04758 | 33513761 | Metabolites | Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. | Details |
| A04892 | 33464703 | Diabetes Obes Metab | Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial. | Details |
| A05156 | 33352183 | Eur J Pharmacol | The effects of glucagon-like peptide-1 receptor agonists on glycemic control and anthropometric profiles among diabetic patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. | Details |
| A05535 | 33216087 | Food Funct | Amelioration of non-alcoholic fatty liver disease by sodium butyrate is linked to the modulation of intestinal tight junctions in db/db mice. | Details |
| A06320 | 32930541 | Eur J Histochem | β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet. | Details |
| A06401 | 32892547 | Turk J Med Sci | Exenatide improves cardiovascular risk factors in obese patients with type 2 diabetes mellitus: a prospective study | Details |
| A06484 | 32862405 | Endocrine | PNPLA3 I148M is involved in the variability in anti-NAFLD response to exenatide. | Details |
| A06633 | 32800550 | Biochem Biophys Res Commun | Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling. | Details |