- |||||||||| pioglitazone / Generic mfg.
Trial completion date, Trial primary completion date: PIOGAS: Pioglitazone for Idiopathic Gastroparesis (clinicaltrials.gov) - Mar 10, 2022
P1, N=10, Recruiting,
This meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF. Trial completion date: Sep 2022 --> Oct 2024 | Trial primary completion date: Sep 2022 --> Sep 2024
- |||||||||| selonsertib (GS-4997) / Gilead, Victoza (liraglutide) / Novo Nordisk, Ocaliva (obeticholic acid) / Intercept
Journal, Gold standard: Non-alcoholic fatty liver disease and steatohepatitis: state-of-the-art on effective therapeutics based on the gold standard method for diagnosis. (Pubmed Central) - Mar 8, 2022
Other drugs including bicyclol, cysteamine bitartrate, L-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins each had a single clinical study. There is an urgent need for further research in this field.
- |||||||||| pioglitazone / Generic mfg.
Central vs Local Stroke Adjudication in the IRIS Trial ([VIRTUAL]) - Mar 6, 2022 - Abstract #AAN2022AAN_1725;
Adjudication by an independent panel of neurologists did not affect the main findings of the IRIS trial. If a panel of independent neurologists is used for outcome classification, it may be most helpful when questions are regarding transient symptoms.
- |||||||||| Suglat (ipragliflozin) / EMD Serono, Kotobuki, Astellas
Clinical, Journal: Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD. (Pubmed Central) - Mar 5, 2022
Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.
- |||||||||| pioglitazone / Generic mfg.
Preclinical, Journal: Effect of parthenolide, an NLRP3 inflammasome inhibitor, on insulin resistance in high-fat diet-obese mice. (Pubmed Central) - Mar 5, 2022
Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) - induced elevation of tumor necrosis factor-α and interleukin-1β in mouse peritoneal macrophages in a dose-dependent manner...Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.
- |||||||||| pioglitazone / Generic mfg.
Clinical, Journal: TRIB3 is highly expressed in the adipose tissue of obese patients and is associated with insulin resistance. (Pubmed Central) - Mar 3, 2022
Our findings support an immunomodulatory strategy to recruit native NSPCs as a potential acute care intervention for SCI.Level of Evidence: N/A. Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that the increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Journal: The mechanisms and therapeutic targets of ferroptosis in cancer. (Pubmed Central) - Mar 3, 2022
Thus, new FINs with high selectivity and bioavailability are required to target tumor cells more specifically and potently. Particularly, the combination of FINs with chemotherapy, radiotherapy, targeted therapy, and immunotherapy warrants clinical investigation in the future.
- |||||||||| pioglitazone / Generic mfg.
Trial initiation date, Trial primary completion date: Effects of Pioglitazone on Stress Reactivity and Alcohol Craving (clinicaltrials.gov) - Mar 2, 2022
P1/2, N=60, Not yet recruiting,
Particularly, the combination of FINs with chemotherapy, radiotherapy, targeted therapy, and immunotherapy warrants clinical investigation in the future. Initiation date: Nov 2021 --> Mar 2022 | Trial primary completion date: Nov 2021 --> Oct 2023
- |||||||||| progesterone / Generic mfg., pioglitazone / Generic mfg.
Review, Journal: Hormesis and Endothelial Progenitor Cells. (Pubmed Central) - Mar 1, 2022
Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone. In general, these studies demonstrate the capacity of these agents to enhance EPC proliferation and angiogenesis functional applications, having a focus on repairing endothelial tissue damage due to acute injury (e.g., stroke), as well as damage from chronic conditions (e.g., atherosclerosis) and normal aging processes.
- |||||||||| doxycycline / Generic mfg., pioglitazone / Generic mfg.
Journal: A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease. (Pubmed Central) - Feb 26, 2022
To validate a small-molecule screening approach, we treated HFD-fed fish with pioglitazone, a drug shown to be beneficial for NAFLD in humans, and measured a sharp reduction in liver lipid accumulation. These results demonstrate new utility for zebrafish in modeling early NAFLD pathogenesis and demonstrate their feasibility for in vivo screening of new pharmacological interventions.
- |||||||||| pioglitazone / Generic mfg., rosiglitazone / Generic mfg.
Preclinical, Journal: Different sites of actions make different responses to thiazolidinediones between mouse and rat models of fatty liver. (Pubmed Central) - Feb 25, 2022
Pioglitazone (PGZ), a thiazolidinedione (TZD) that acts via peroxisome proliferator activated receptor gamma (PPARγ) is the only agent that has shown consistent benefit and efficacy in clinical trials...Therefore, we compared the effects of TZDs including PGZ and rosiglitazone (RGZ) in ob/ob mice and Lep/Lep rats, models of leptin-deficient obesity, and A-ZIP/F-1 mice and seipin knockout (SKO) rats, models of generalized lipodystrophy...Although the response to TZDs in mice is the complete opposite of that in human patients, no report has pointed out the problem with TZD studies using mouse models so far. The present study might provide useful suggestions in research on TZDs.
- |||||||||| pioglitazone / Generic mfg.
Preclinical, Journal: Hypoglycemic and Hypolipidemic Swords: Synthesis and In-vivo Biological Assessment of 5-benzylidene-2,4-thiazolidinediones. (Pubmed Central) - Feb 24, 2022
Four synthetic molecules (V2, V4, V5, and V20) possessed significant hypoglycaemic and hypolipidemic activity as compared to the positive control pioglitazone...Two representative compounds V2 and V4, were evaluated for their PPARγ activation potential, demonstrating that they were partial PPARγ agonists, thus confirming our designing hypothesis. Based on the results obtained, we assume that these compounds have the potential to be developed as future antidiabetic agents.
- |||||||||| pioglitazone / Generic mfg.
Clinical, Journal: Clinically relevant mitochondrial-targeted therapy improves chronic outcomes after traumatic brain injury. (Pubmed Central) - Feb 23, 2022
Finally, we demonstrate that delayed pioglitazone treatment improves serial motor and cognitive performance in conjunction with attenuated brain atrophy after traumatic brain injury. This study illustrates that mitoNEET is the critical target for delayed pioglitazone intervention after traumatic brain injury, mitochondrial-targeting is highly time-dependent after injury and there is an extended therapeutic window to effectively treat mitochondrial dysfunction after brain injury.
- |||||||||| pioglitazone / Generic mfg.
Journal: A role for peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists in counteracting the degeneration of cardiovascular grafts. (Pubmed Central) - Feb 22, 2022
Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves...Interestingly, significantly increased intima hyperplasia could be observed in PIO compared to controls after 12 weeks (p=0.017).Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in aortic valve conduits, and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.
- |||||||||| Victoza (liraglutide) / Novo Nordisk
Journal: The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD. (Pubmed Central) - Feb 19, 2022
To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for. A paradigm change is developing between the endocrinologist's greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.
- |||||||||| rifampicin / Generic mfg.
Preclinical, Journal: Investigating the Utility of Humanized PXR-CAR-CYP3A4/7 Mouse Model to Assess CYP3A-Mediated Induction. (Pubmed Central) - Feb 16, 2022
The work presented here showcases the Tg-Composite model which was able to recapitulate the magnitude of clinical induction and to differentiate tissue dependent induction observed with rifampin, but not with efavirenz. These results not only foreshadow the potential application of such transgenic models in assessing clinical induction, but also in further investigating the mechanism of drug disposition.
- |||||||||| Retrospective data, Review: Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis. (Pubmed Central) - Feb 16, 2022
Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference...Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits...When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
- |||||||||| celecoxib oral / Generic mfg.
Review, Journal: Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer's disease. (Pubmed Central) - Feb 12, 2022
Non-selective COX inhibitor indomethacin is also potent inhibitor of inflammatory mediators released from microglia...Mitophagy induction is also beneficial in the removal of damaged mitochondria and reduction of infiltration of inflammatory molecules at the site of accumulation of the damaged mitochondria. Targeting these pathways and eventually ameliorating the activation of microglia can mitigate neuroinflammation and come out as a better therapeutic option for the treatment of Alzheimer's disease.
- |||||||||| aspirin / Generic mfg., pioglitazone / Generic mfg., clopidogrel / Generic mfg.
Review, Journal: Stroke Prevention: Little-Known and Neglected Aspects. (Pubmed Central) - Feb 11, 2022
These include the following: (1) implementation of a Mediterranean diet; (2) B vitamins to lower homocysteine; (3) coordinated approaches to smoking cessation; (4) intensive lipid-lowering therapy; (5) lipid lowering in the elderly; (6) physiologically individualized therapy for hypertension based on renin/aldosterone phenotyping; (7) avoiding excessive blood pressure reduction in patients with stiff arteries; (8) treatment of insulin resistance with pioglitazone in stroke patients with prediabetes and diabetes; (9) impaired activation of clopidogrel in patients with variants of CYP2C19; (10) aspirin pseudoresistance due to enteric coating; (11) rationale for anticoagulation in patients with embolic stroke of unknown source; (12) pharmacologic properties of direct-acting oral anticoagulants that should be considered when choosing among them; (13) the identification of which patients with asymptomatic carotid stenosis are at a high enough risk to benefit from carotid endarterectomy or stenting; and (14) the importance of age in choosing between endarterectomy and stenting. Stroke prevention could be improved by better recognition of these issues and by implementation of the principles derived from them.
- |||||||||| pioglitazone / Generic mfg.
Preclinical, Journal: Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery. (Pubmed Central) - Feb 11, 2022
In a separate group, after 4 months of HFD, mice were treated with pioglitazone (PIO) or 4-phenylbutyric acid for the last month...There was also a reduction in circulating adiponectin and in perivascular adiponectin expression in the pulmonary artery, associated with a reduction in PPAR-γ expression. Treatment with PIO improved IR and PH and reversed the lower expression of adiponectin and PPAR-γ in the pulmonary artery, highlighting this drug as potential benefit for this poorly recognized complication of obesity.
- |||||||||| pioglitazone / Generic mfg.
Journal: Pioglitazone reduces the incidence of Alzheimer's disease: From genetics to population-based validation. (Pubmed Central) - Feb 4, 2022
Restoration of pTyr14cav-1 did not lead to amelioration of the disease, nor did it prevent RV hypertrophy and fibrosis, which was indicated by an increase in Acta2, Nppb, Col3a1, and Tgfβ1 mRNA. In summary, we present an integrated, network-based methodology to rapidly translate GWAS findings and multi-omics data to genotype-informed therapeutic discovery in AD.
- |||||||||| rosuvastatin / Generic mfg.
Journal: HbA1c, Coronary atheroma progression and cardiovascular outcomes. (Pubmed Central) - Feb 4, 2022
Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Trial completion date, Trial primary completion date: Dapagliflozin Plus Pioglitazone in T1DM (clinicaltrials.gov) - Feb 4, 2022
P4, N=120, Recruiting,
These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
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