Investigational Drug Details
| Drug ID: | D275 |
| Drug Name: | Pioglitazone |
| Synonyms: | (±)-5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-2,4-thiazolidinedione; 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione; Pioglitazone |
| Type: | Chemical drug |
| DrugBank ID: | DB01132 |
| DrugBank Description: | Pioglitazone is an antihyperglycemic used as an adjunct to diet, exercise, and other antidiabetic medications to manage type 2 diabetes mellitus. It is administered as a racemic mixture, though there is no pharmacologic difference between the enantiomers and they appear to interconvert _in vivo_ with little consequence. The thiazolidinedione class of medications, which also includes and , exerts its pharmacological effect primarily by promoting insulin sensitivity and the improved uptake of blood glucose via agonism at the peroxisome proliferator-activated receptor-gamma (PPARγ). PPARs are ligand-activated transcription factors that are involved in the expression of more than 100 genes and affect numerous metabolic processes, most notably lipid and glucose homeostasis. Thiazolidinediones, including pioglitazone, have fallen out of favor in recent years due to the presence of multiple adverse effects and warnings regarding their use (e.g. congestive heart failure, bladder cancer) and the availability of safer and more effective alternatives for patients with type 2 diabetes mellitus. |
| PubChem ID: | 4829 |
| CasNo: | 111025-46-8 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)C[C@@]3([H])SC(NC3=O)=O |
| Structure: |
|
| InChiKey: | HYAFETHFCAUJAY-QGZVFWFLSA-N |
| Molecular Weight: | 356.447 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor gamma agonist; Amine oxidase [flavin-containing] B inhibitor |
| DrugBank MoA: | Pioglitazone is a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ increases the transcription of insulin-responsive genes involved in the control of glucose and lipid production, transport, and utilization. Through this mechanism, pioglitazone both enhances tissue sensitivity to insulin and reduces the hepatic production of glucose (i.e. gluconeogenesis) - insulin resistance associated with type 2 diabetes mellitus is therefore improved without an increase in insulin secretion by pancreatic beta cells. |
| DrugBank Pharmacology: | Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis. In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values. Significant fluid retention leading to the development/exacerbation of congestive heart failure has been reported with pioglitazone - avoid its use in patients in heart failure or at risk of developing heart failure. There is some evidence that pioglitazone may be associated with an increased risk of developing bladder cancer. Pioglitazone should not be used in patients with active bladder cancer and should be used with caution in patients with a history of bladder cancer. |
| DrugBank Indication: | Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also available in combination with , , or for the same indication. |
| Targets: | PPARG agonist |
| Therapeutic Category: | Improve insulin resistance |
| Clinical Trial Progress: | Phase 3 completed (NCT00063622: Pioglitazone led to significant improvements in hepatic steatosis, inflammation, insulin resistance, and liver enzyme levels in the phase III.) |
| Latest Progress: | Advanced in clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0050 | NCT03646292 | Phase 4 | Recruiting | No Results Available | December 19, 2018 | October 19, 2020 | Details |
| L0054 | NCT03910361 | Phase 4 | Completed | No Results Available | April 12, 2019 | April 29, 2021 | Details |
| L0067 | NCT03796975 | Phase 4 | Completed | No Results Available | June 28, 2018 | August 7, 2020 | Details |
| L0068 | NCT02875821 | Phase 4 | Completed | No Results Available | April 26, 2016 | June 23, 2017 | Details |
| L0099 | NCT01431521 | Phase 1 | Completed | Has Results | October 26, 2011 | September 10, 2018 | Details |
| L0101 | NCT01289639 | Not applicable | Terminated | Has Results | October 2005 | August 17, 2017 | Details |
| L0103 | NCT02365233 | Phase 4 | Terminated | Has Results | May 1, 2013 | July 31, 2018 | Details |
| L0104 | NCT02265276 | Phase 3 | Unknown status | No Results Available | October 2014 | October 16, 2014 | Details |
| L0113 | NCT04976283 | Phase 4 | Recruiting | No Results Available | September 15, 2021 | March 18, 2022 | Details |
| L0120 | NCT00994682 | Phase 4 | Completed | Has Results | December 2008 | April 5, 2017 | Details |
| L0181 | NCT00013598 | Phase 2 | Completed | No Results Available | March 2001 | March 4, 2008 | Details |
| L0184 | NCT05254626 | Phase 4 | Not yet recruiting | No Results Available | March 2022 | February 24, 2022 | Details |
| L0233 | IRCT20190122042450N3 | Phase 2/Phase 3 | Not Recruiting | No Results Available | 24/05/2019 | 26 August 2019 | Details |
| L0255 | NCT00227110 | Phase 4 | Completed | No Results Available | October 2002 | October 14, 2009 | Details |
| L0335 | NCT03950505 | Phase 4 | Recruiting | No Results Available | May 29, 2020 | October 9, 2020 | Details |
| L0404 | IRCT20190122042450N5 | Phase 2 | Recruiting | No Results Available | 29/11/2020 | 5 January 2021 | Details |
| L0409 | IRCT20190701044062N3 | Phase 3 | Recruiting | No Results Available | 16/09/2020 | 6 October 2020 | Details |
| L0423 | NCT04501406 | Phase 2 | Recruiting | No Results Available | 03/08/2020 | 25 January 2021 | Details |
| L0478 | JPRN-jRCTs031180159 | Not applicable | Not Recruiting | Has Results | 26/02/2019 | 10 January 2022 | Details |
| L0516 | JPRN-UMIN000030548 | Not applicable | Not Recruiting | No Results Available | 25/12/2017 | 2 April 2019 | Details |
| L0517 | JPRN-UMIN000030355 | Not applicable | Recruiting | No Results Available | 15/12/2017 | 17 May 2021 | Details |
| L0578 | IRCT2015120819554N10 | Phase 3 | Not Recruiting | No Results Available | 12/07/2016 | 22 February 2018 | Details |
| L0581 | JPRN-UMIN000022651 | Not selected | Not Recruiting | No Results Available | 07/06/2016 | 2 April 2019 | Details |
| L0588 | JPRN-UMIN000021291 | Not selected | Not Recruiting | No Results Available | 02/03/2016 | 2 April 2019 | Details |
| L0615 | IRCT201309188308N3 | Phase 3 | Not Recruiting | No Results Available | 23/02/2015 | 22 February 2018 | Details |
| L0639 | IRCT2013071313069N2 | Phase 3 | Not Recruiting | No Results Available | 22/09/2013 | 22 February 2018 | Details |
| L0664 | IRCT201105026361N1 | Phase 2 | Not Recruiting | No Results Available | 16/11/2011 | 22 February 2018 | Details |
| L0692 | JPRN-UMIN000001035 | Not applicable | Not Recruiting | No Results Available | 15/02/2008 | 2 April 2019 | Details |
| L0730 | IRCT20150706023083N2 | Phase 3 | Not Recruiting | No Results Available | 23/09/2019 | 5 November 2019 | Details |
| L0763 | NCT00063622 | Phase 3 | Not recruiting | Has Results | 01/07/2003 | 12 December 2020 | Details |
| L0780 | IRCT20180404039187N1 | Phase 2/Phase 3 | Recruiting | No Results Available | 22/11/2018 | 14 January 2019 | Details |
| L0820 | IRCT201705016312N4 | Not applicable | Not Recruiting | No Results Available | 20/05/2017 | 22 February 2018 | Details |
| L0853 | IRCT2016010411991N3 | Not applicable | Not Recruiting | No Results Available | 22/01/2016 | 22 February 2018 | Details |
| L0910 | ISRCTN33414972 | Not applicable | Not Recruiting | No Results Available | 16/12/2013 | 27 February 2017 | Details |
| L0929 | NCT01703260 | Phase 2 | Not recruiting | Has Results | 02/10/2012 | 19 October 2017 | Details |
| L0954 | IRCT201105084849N2 | Phase 3 | Not Recruiting | No Results Available | 28/05/2011 | 22 February 2018 | Details |
| L0960 | NCT01068444 | Phase 2 | Not recruiting | No Results Available | 11/02/2010 | 12 December 2020 | Details |
| L0964 | NCT01002547 | Phase 4 | Not recruiting | Has Results | 23/10/2009 | 12 December 2020 | Details |
| L0977 | NCT00633282 | Phase 2 | Not recruiting | No Results Available | 03/03/2008 | 19 February 2015 | Details |
| L0988 | NCT00062764 | Phase 2 | Not recruiting | Has Results | 12/06/2003 | 19 October 2017 | 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 | |
|---|---|---|---|---|
| A00004 | 35258780 | Chin J Integr Med | Protective Roles of Shilajit in Modulating Resistin, Adiponectin, and Cytokines in Rats with Non-alcoholic Fatty Liver Disease. | Details |
| A00027 | 35250889 | Front Endocrinol (Lausanne) | Corrigendum: Pioglitazone for NAFLD Patients With Prediabetes or Type 2 Diabetes Mellitus: A Meta-Analysis. | Details |
| A00034 | 35249505 | Curr Drug Saf | Pioglitazone, Bladder Cancer and the Presumption of Innocence. | Details |
| A00162 | 35203687 | Biomedicines | A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease. | Details |
| A00446 | 35080048 | J Gastroenterol Hepatol | Malaysian Society of Gastroenterology and Hepatology consensus statement on metabolic dysfunction-associated fatty liver disease. | 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 |
| A00609 | 35030323 | Lancet Gastroenterol Hepatol | Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. | Details |
| A00616 | 35027111 | J Am Coll Cardiol | Risk of Heart Failure in Patients With Nonalcoholic Fatty Liver Disease: JACC Review Topic of the Week. | Details |
| A00651 | 35014161 | Diabetes Obes Metab | The metabolic triad of non-alcoholic fatty liver disease, visceral adiposity and type 2 diabetes: Implications for treatment. | 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 |
| A00656 | 35013417 | Sci Rep | Different sites of actions make different responses to thiazolidinediones between mouse and rat models of fatty liver. | Details |
| A01118 | 34863942 | Mol Metab | The metabolic syndrome, thiazolidinediones, and implications for intersection of chronic and inflammatory disease. | Details |
| A01137 | 34858740 | Cureus | Pioglitazone for the Treatment of Metabolic-Associated Fatty Liver Disease in People Living With HIV and Prediabetes. | Details |
| A01147 | 34855339 | FP Essent | Liver Disease: Nonalcoholic Fatty Liver Disease. | Details |
| A01575 | 34688168 | Curr Opin Pharmacol | Non-alcoholic fatty liver disease: Current therapeutic options. | Details |
| A01843 | 34593018 | BMC Pharmacol Toxicol | Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis. | Details |
| A01937 | 34558835 | Hepatol Commun | Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD. | Details |
| A02124 | 34497708 | Ther Adv Endocrinol Metab | Therapeutic approaches for non-alcoholic steatohepatitis. | Details |
| A02209 | 34459761 | Wiad Lek | ASSOCIATION ANALYSIS OF PIOGLITAZONE EFFECTIVENESS IN TREATMENT OF NAFLD PATIENTS WITH OBESITY AND PPARG RS1801282 (PRO12ALA) GENOTYPE. | Details |
| A02287 | 34435378 | Aliment Pharmacol Ther | Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH. | Details |