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Hepatology Communications Sep 2022The incidence of nonalcoholic fatty liver disease (NAFLD) has recently increased and is related to obesity and the associated surge in type 2 diabetes mellitus (T2DM)... (Randomized Controlled Trial)
Randomized Controlled Trial
The incidence of nonalcoholic fatty liver disease (NAFLD) has recently increased and is related to obesity and the associated surge in type 2 diabetes mellitus (T2DM) and metabolic syndromes. This trial follows up on our previous work and forms part of the ToPiND study. We aimed to combine tofogliflozin and pioglitazone treatment for hepatic steatosis in patients with NAFLD and T2DM. In this open-label, prospective, single-center, randomized clinical trial, patients with NAFLD with T2DM and a hepatic fat fraction of ≥10% were assessed based on magnetic resonance imaging proton density fat fraction. Eligible patients received either 20 mg tofogliflozin or 15-30 mg pioglitazone orally, once daily for 24 weeks, followed by combination therapy with both medicines for an additional 24 weeks. The effects on diabetes mellitus and hepatic steatosis were examined at baseline and after the completion of monotherapy and combination therapy. Thirty-two eligible patients received the combination therapy of tofogliflozin and pioglitazone. The combination therapy showed additional improvement in glycated hemoglobin compared with each monotherapy group and showed improvement in steatosis, hepatic stiffness, and alanine aminotransferase levels compared with the tofogliflozin monotherapy group. Pioglitazone monotherapy-mediated increase in body weight decreased following concomitant use of tofogliflozin. The combination therapy resulted in lower triglyceride, higher high-density lipoprotein cholesterol, higher adiponectin, and higher ketone body levels. Conclusion: In addition to the additive effects of tofogliflozin and pioglitazone in patients with T2DM and NAFLD, combination therapy was suggested to reduce weight gain and induce cardioprotective effect. Further studies with more patients are needed to investigate the combination therapy of various drugs.
Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prospective Studies
PubMed: 35578445
DOI: 10.1002/hep4.1993 -
BMJ Open Diabetes Research & Care Nov 2023Metabolic dysfunction-associated steatohepatitis (MASH) is highly prevalent in type 2 diabetes (T2D). Pioglitazone and glucagon-like peptide-1 receptor agonists...
INTRODUCTION
Metabolic dysfunction-associated steatohepatitis (MASH) is highly prevalent in type 2 diabetes (T2D). Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) are medications used in T2D that can resolve MASH and should be considered in all patients with T2D and MASH. We assessed prescription rates of evidence-based T2D pharmacotherapy (EBP) in MASH, and ascertained racial/ethnic disparities in prescribing.
RESEARCH DESIGN AND METHODS
We conducted a cross-sectional study on patients in Duke University Health System with diagnosis codes for T2D and MASH between January 2019 and January 2021. Only patients with ≥1 primary care or endocrinology encounter were included. The primary outcome was EBP, defined as ≥1 prescription for pioglitazone and/or a GLP-1RA during the study period. A multivariable logistic regression model was used to examine the primary outcome.
RESULTS
A total of 847 patients with T2D and MASH were identified; mean age was 59.7 (SD 12) years, 61.9% (n=524) were female, and 11.9% (n=101) and 4.6% (n=39) were of Black race and Latino/a/x ethnicity, respectively. EBP was prescribed in 34.8% (n=295). No significant differences were noted in the rates of EBP use across racial/ethnic groups (Latino/a/x vs White patients: adjusted OR (aOR) 1.82, 95% CI 0.78 to 4.28; Black vs White patients: aOR 0.76, 95% CI 0.44 to 1.33, p=0.20).
CONCLUSIONS
EBP prescriptions, especially pioglitazone, are low in patients with T2D and MASH, regardless of race/ethnicity. These data underscore the need for interventions to close the gap between current and evidence-based care.
Topics: Female; Humans; Male; Middle Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ethnicity; Hispanic or Latino; Pioglitazone; Black or African American; White; Aged; Glucagon-Like Peptide-1 Receptor; Fatty Liver
PubMed: 38030391
DOI: 10.1136/bmjdrc-2023-003763 -
Molecular Genetics & Genomic Medicine Mar 2023Although pioglitazone, a well-known anti-diabetic agent, has recently established itself as a pillar of cancer treatment, its therapeutic value could be attenuated by...
BACKGROUND
Although pioglitazone, a well-known anti-diabetic agent, has recently established itself as a pillar of cancer treatment, its therapeutic value could be attenuated by the aberrant activation of the PI3K/Akt pathway.
AIM
To evaluate whether the PI3K/Akt suppression in leukemic cells could potentiate the anti-leukemic effects of pioglitazone.
METHODS
To assess the anti-leukemic effects of PI3K/Akt inhibitors on anti-leukemic effects of pioglitazone, we used MTT and trypan blue assays. Flow cytometric analysis and qRT-PCR were also applied to evaluate cell cycle and apoptosis.
RESULT
The resulting data revealed that upon PPARγ stimulation in different leukemic cell lines using pioglitazone, the survival and the proliferative capacity of the cells were significantly halted. Then, we evaluated the impact of the PI3K/Akt axis on the effectiveness of the drug in the most sensitive leukemic cell line; NB4 cells. Our results showed that treatment of NB4 cells with the PI3K inhibitors increased the sensitivity of leukemic cells to pioglitazone to the degree that even lower concentrations of the agent succeeded to induce apoptotic as well as the anti-proliferative effects. Moreover, it seems that PI3K inhibition could potentiate the anti-leukemic effect of pioglitazone through induction of p21-mediated sub-G1 cell cycle arrest and altering the balance between the pro-and anti-apoptotic genes.
CONCLUSION
This study sheds light on the significance of the PI3K/Akt pathway in APL cell sensitivity to pioglitazone and proposed that the presence of the PI3K inhibitor in the therapeutic regimen containing pioglitazone could be promising in the treatment of this malignancy.
Topics: Humans; Apoptosis; Leukemia, Promyelocytic, Acute; Phosphatidylinositol 3-Kinases; Pioglitazone; Proto-Oncogene Proteins c-akt; Protein Kinase Inhibitors
PubMed: 36398521
DOI: 10.1002/mgg3.2106 -
International Immunopharmacology Nov 2023Thalamic pain frequently occurs after stroke and is a challenging clinical issue. However, the mechanisms underlying thalamic pain remain unclear. Neuroinflammation is a...
BACKGROUND
Thalamic pain frequently occurs after stroke and is a challenging clinical issue. However, the mechanisms underlying thalamic pain remain unclear. Neuroinflammation is a key determining factor in the occurrence and maintenance of hemorrhage-induced thalamic pain. Pioglitazone is an agonist of peroxisome proliferator-activated receptor gamma (PPARγ) and shows anti-inflammatory effects in multiple diseases. The present work focused on exploring whether PPARγ is related to hemorrhage-induced thalamic pain.
METHODS
Immunostaining was conducted to analyze the cellular localization of PPARγ and co-localization was evaluated with NeuN, ionized calcium-binding adapter molecular 1 (IBA1), and glia fibrillary acidic protein (GFAP). Western blot analyses were used to evaluate MyD88, pNF-κB/NF-κB, pSTAT6/STAT6, IL-1β, TNF-α, iNOS, Arg-1, IL-4, IL-6, and IL-10 expression. Behavioral tests in mice were conducted to evaluate continuous pain hypersensitivity.
RESULTS
We found that pioglitazone appeared to mitigate the contralateral hemorrhage-induced thalamic pain while inhibiting inflammatory responses. Additionally, Pioglitazone induced phosphorylation of STAT6 and suppressed the phosphorylation NF-κB in our model of thalamic pain. These effects could be partially reversed with the PPARγ antagonist GW9662.
CONCLUSION
The PPARγ agonist pioglitazone can mitigate mechanical allodynia by suppressing the NF-κB inflammasome while activating the STAT6 signal pathway, which are well-known to be associated with inflammation.
Topics: Mice; Animals; Pioglitazone; PPAR gamma; Thiazolidinediones; NF-kappa B; Neuroinflammatory Diseases; PPAR-gamma Agonists; Hemorrhage; Pain
PubMed: 37774485
DOI: 10.1016/j.intimp.2023.110991 -
Biochemical and Biophysical Research... Aug 2023Iron-sulfur clusters play a central role in cellular function and are regulated by the ATM protein. Iron-sulfur clusters are part of the cellular sulfide pool, which...
BACKGROUND
Iron-sulfur clusters play a central role in cellular function and are regulated by the ATM protein. Iron-sulfur clusters are part of the cellular sulfide pool, which functions to maintain cardiovascular health, and consists of free hydrogen sulfide, iron-sulfur clusters, protein bound sulfides, which constitute the total cellular sulfide fraction. ATM protein signaling and the drug pioglitazone share some cellular effects, which led us to examine the effects of this drug on cellular iron-sulfur cluster formation. Additionally, as ATM functions in the cardiovasculature and its signaling may be diminished in cardiovascular disease, we examined pioglitazone in the same cell type, with and without ATM protein expression.
METHODS
We examined the effects of pioglitazone treatment on the total cellular sulfide profile, the glutathione redox state, cystathionine gamma-lyase enzymatic activity, and on double-stranded DNA break formation in cells with and without ATM protein expression.
RESULTS
Pioglitazone increased the acid-labile (iron-sulfur cluster) and bound sulfur cellular fractions and reduced cystathionine gamma-lyase enzymatic activity in cells with and without ATM protein expression. Interestingly, pioglitazone also increased reduced glutathione and lowered DNA damage in cells without ATM protein expression, but not in ATM wild-type cells. These results are interesting as the acid-labile (iron-sulfur cluster), bound sulfur cellular fractions, and reduced glutathione are low in cardiovascular disease.
CONCLUSION
Here we found that pioglitazone increased the acid-labile (iron-sulfur cluster) and bound sulfur cellular fractions, impinges on hydrogen sulfide synthesis, and exerts beneficial effect on cells with deficient ATM protein signaling. Thus, we show a novel pharmacologic action for pioglitazone.
Topics: Humans; Hydrogen Sulfide; Ataxia Telangiectasia Mutated Proteins; Pioglitazone; Cystathionine gamma-Lyase; Cardiovascular Diseases; Sulfides; Sulfur; Glutathione; Iron; Iron-Sulfur Proteins
PubMed: 37285721
DOI: 10.1016/j.bbrc.2023.05.118 -
Pathogens and Global Health Oct 2023This study examines the effects of three different drugs with metformin, acarbose and pioglitazone active ingredients used for antidiabetic purposes on cysts and...
This study examines the effects of three different drugs with metformin, acarbose and pioglitazone active ingredients used for antidiabetic purposes on cysts and trophozoites. Cultures of trophozoites and cysts were prepared to test the anti-amoebic activity of metformin, acarbose and pioglitazone. Cultures were then prepared for cyst and trophozoite forms and parasites were exposed to different concentrations (0.750 mg/mL, 0.375 mg/mL, 0.186 mg/mL and 0.093 mg/mL) of metformin, acarbose and pioglitazone. As a result of the study, the reproductive potential suppressive effects and conversion from trophozoite form to cyst form of all three substances on trophozoites and cysts were determined. Parasites were counted at 12, 24 and 48 hours in the cell counter after staining with trypan blue. In comparison of the effects of metformin, acarbose and pioglitazone used in the study on trophozoites and cysts, it was observed that all three substances were statistically effective against cysts and trophozoites at a concentration of 0.750 mg/mL. Furthermore, it was determined that all concentrations of the three active substances included in the study significantly decreased the rate of cyst formation even at the end of the 7th day. In this context, it was determined that all three substances have amebicidal effects, and they significantly inhibit the transformation of trophozoites to cyst form. It is thought that these active substances, which are currently used as anti-diabetic, can be used in combination with other drugs in infections based on our study findings.
Topics: Animals; Trophozoites; Acanthamoeba castellanii; Hypoglycemic Agents; Acarbose; Pioglitazone; Metformin
PubMed: 36436006
DOI: 10.1080/20477724.2022.2151859 -
Scientific Reports Apr 2021Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day... (Comparative Study)
Comparative Study
Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day pioglitazone, low dose of pioglitazone + carvacrol and 0.03 mg/kg/day dexamethasone (Dexa) for 16 days after the end of PQ exposure were studied (n = 6 in each group). Lung pathological changes, tracheal responsiveness to methacholine and ovalbumin (OVA) as well as transforming growth factor beta (TGF-β) and interleukin (IL)-6 level in the lung tissue homogenize as well as TGF-β, IL-6, oxidant and antioxidant levels oxidant and antioxidants were increased in PQ group (p < 0.01 to p < 0.001). Lung pathological changes, tracheal responsiveness to methacholine and OVA as well as TGF-β, IL-6 oxidant and antioxidant levels were improved in all treated groups except lung pathological changes in treated group with low dose of pioglitazone (p < 0.05 to p < 0.001). The effects of low dose of pioglitazone and carvacrol alone were significantly lower than in the combination group of low dose of pioglitazone + carvacrol (p < 0.05 to p < 0.001). Carvacrol treatment improved inhaled PQ-induced lug injury similar to the effects of dexamethasone. The synergic effect of carvacrol and pioglitazone suggests PPAR-γ receptor mediated effects of carvacrol on inhaled PQ-induced lung injury.
Topics: Animals; Case-Control Studies; Cymenes; Dexamethasone; Disease Models, Animal; Drug Synergism; Gene Expression Regulation; Interleukin-6; Lung Injury; Male; Oxidative Stress; Paraquat; Pioglitazone; Rats; Rats, Wistar; Transforming Growth Factor beta; Treatment Outcome
PubMed: 33854134
DOI: 10.1038/s41598-021-87546-8 -
European Journal of Neurology Feb 2021The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin...
BACKGROUND AND PURPOSE
The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin treatment on prevention of PD. This study analyzed the associations between pioglitazone, statins, and the incidence of PD in patients with diabetes mellitus (DM) in Taiwan.
METHODS
We used the National Health Insurance database from 1996 to 2013. DM and PD were diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used the propensity score-matching method to match the study groups. Cox regression analyses were employed to calculate the relative risk of the incidence of PD.
RESULTS
There were 48 828 patients matched and categorized equally into the pioglitazone group and the non-pioglitazone group. The number of PD patients in the pioglitazone group and the non-pioglitazone group was 275 (1.1%) and 417 (1.7%), respectively. The pioglitazone group had a lower incidence of PD, with an adjusted hazard ratio (aHR) of 0.66 [95% confidence interval (CI): 0.57-0.78], and this benefit was dose-dependent. Of note, as compared with either pioglitazone or statin treatment, our results first showed that the combination of pioglitazone and statins further lowered the risk of PD, with an aHR of 0.78 (95% CI: 0.64-0.94; P = 0.010).
CONCLUSIONS
Our study results suggested that pioglitazone could be a promising agent for reducing the incidence of PD in patients with DM, and works synergistically with statins.
Topics: Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Parkinson Disease; Pioglitazone; Retrospective Studies; Risk Factors; Taiwan
PubMed: 32969141
DOI: 10.1111/ene.14542 -
Diabetes Research and Clinical Practice Jun 2023To evaluate the effect of SGLT2is, pioglitazone, and their combination on the risk of major adverse cardiovascular events (MACE) and heart failure in type 2 diabetes...
Pioglitazone, SGLT2 inhibitors and their combination for primary prevention of cardiovascular disease and heart failure in type 2 diabetes: Real-world evidence from a nationwide cohort database.
OBJECTIVE
To evaluate the effect of SGLT2is, pioglitazone, and their combination on the risk of major adverse cardiovascular events (MACE) and heart failure in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease.
RESEARCH DESIGN AND METHODS
Using Taiwan National Health Insurance Research Database, we identified four groups based on medication use, including 1) both SGLT2is and pioglitazone, 2) SGLT2i, 3) pioglitazone and 4) non-study drugs (reference group). The four groups were matched by propensity score. The primary outcome was 3-point MACE, which included myocardial infarction, stroke, cardiovascular death, and the secondary outcome was incidence of heart failure.
RESULTS
After propensity-matching, each group included 15,601 patients. Compared with the reference group, the pioglitazone/SGLT2i combination group had a significantly lower risk for MACE (aHR 0.76, 95 % CI 0.66-0.88) and heart failure (aHR 0.67, 95 % CI 0.55-0.82). Pioglitazone was associated with a lower risk of MACE (aHR 0.82, 95 % CI 0.71-0.94) and there was no difference in risk of heart failure compared with the reference group. The incidence of heart failure was significantly decreased in the SGLT2i group (aHR 0.7, 95 % CI 0.58-0.86).
CONCLUSION
Combination therapy with pioglitazone and SGLT2is is an effective treatment in the primary prevention of MACE and heart failure in patients with type 2 diabetes.
Topics: Humans; Pioglitazone; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Heart Failure; Primary Prevention
PubMed: 37100230
DOI: 10.1016/j.diabres.2023.110685 -
Pakistan Journal of Pharmaceutical... Mar 2021Diabetics are twice as likely to have depression. It's normal to have long periods of sadness and anxiety. Pioglitazone has important role in the inflammatory response,...
Diabetics are twice as likely to have depression. It's normal to have long periods of sadness and anxiety. Pioglitazone has important role in the inflammatory response, which suggests that it might have the associated anti-depressant effects being manifested by its anti-depressant profile which needs further exploration. Monitoring changes in behavioral and neurochemical profile of pioglitazone in a dose-dependent manner was the purpose of this study. Pioglitazone was injected to rats at the doses of 0mg/kg, 2.5mg/kg, 5mg/kg and 10mg/kg. Behavioral activities in open field, Skinner's box and elevated plus maze were monitored 20, 35 and 45 minutes respectively after pioglitazone injection. whole brain samples were collected following decapitation of rats one-hour after injection. Samples were kept at -70ºC till HPLC-EC analysis for neurochemical profile. Results show anxiogenic and sedative effects of pioglitazone at all three doses as indicated by Skinner's box, elevated plus maze activity and open field. Also there was an overall decreased dopamine metabolism and increased serotonin turnover. This suggests that diabetic patients using pioglitazone as a therapeutic option, may experience more potent effects of CNS depressants. Findings may help in extending therapeutics in diabetic patients suffering from anxiety and/or depression.
Topics: Animals; Behavior, Animal; Brain; Dopamine; Dose-Response Relationship, Drug; Elevated Plus Maze Test; Hypoglycemic Agents; Motor Activity; Open Field Test; Pioglitazone; Rats; Serotonin
PubMed: 34275837
DOI: No ID Found