pioglitazone / Generic mfg. - LARVOL DELTA

Concurrent Thiazolidinediones and GLP-1 Receptor Agonists Therapy in MASH Cirrhosis Patients: A Propensity-Score-Matched Retrospective Cohort Study (ACG 2026) - "Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis carries a significant clinical burden with unmet therapeutic needs... Our retrospective cohort study utilized the TriNetX US Collaborative Network to identify patients with MASH-related cirrhosis (ICD-10: K75.81/K76.0 plus K74.6/K74.69) receiving GLP-1RA/GIP (semaglutide, tirzepatide, liraglutide, exenatide, dulaglutide, or albiglutide) alone or with TZD (pioglitazone or rosiglitazone)... After matching, cohorts were well balanced (mean age 58.5 years; 81% White; 78% T2DM; 10% esophageal varices) except for higher BMI and HbA1c in combination cohort, reflecting TZD use as add-on therapy for refractory hyperglycemia. The combination group demonstrated a 37% relative reduction in all-cause mortality (3.7% vs. 5.1%; risk difference â1.4%, 95% CI â2.4% to â0.4%; p=0.007; HR 0.63, 95% CI 0.50â0.80; log-rank p0.001)."

Retrospective data • CNS Disorders • Diabetes • Fibrosis • Gastroenterology • Hematological Disorders • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease • Solid Tumor • Type 2 Diabetes Mellitus

Phase I/Ib study of inavolisib (INAVO) alone and in combination with endocrine therapy ± palbociclib (PALBO) in patients (pts) with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (HR+, HER2– LA/mBC): Analysis of hyperglycemia (HG) in prediabetic/obese pts. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03006172 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes degradation of mutated p110α, is approved by the FDA in combination with PALBO + fulvestrant (FULV) for PIK3CA-mutated, HR+, HER2–, endocrine-resistant advanced BC... Adults ≥ 18 years of age received INAVO alone (Arm A), + letrozole (LET) + PALBO (Arm B), + LET (Arm C), + FULV (Arm D), + FULV + PALBO (Arm E), or + FULV + PALBO + primary prophylactic metformin (Arm F)...The most common anti-HG medications were metformin (52.7%; biguanide; concomitant use in Arm F excluded), empagliflozin (25.5%; SGLT-2 inhibitor), sitagliptin (22.7%; DPP-4 inhibitor), and pioglitazone (13.6%; thiazolidinedione); insulin was used in 8.2% of pts... A high proportion of prediabetic/obese pts were included in GO39374. In most of these pts, HG was manageable with dose interruptions and oral anti-HG medications, most commonly metformin. Data support the use..."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Obesity • Oncology • Solid Tumor • HER-2 • PIK3CA

L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis. (PubMed, PLoS One) - "L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPARγ-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia."

Journal • Gynecology • IFNG • IL4 • IL6 • PPARG • TNFA

Semaglutide and pioglitazone restore airway mucosal homeostasis by resolving Pseudomonas aeruginosa pyocyanin-induced mucus hypersecretion, ciliostasis, and type 2 airway inflammation. (PubMed, Front Immunol) - "The protective effects of these drugs were partially abolished by respective antagonists, Exendin(9-39) and GW9662, against GLP1R and PPARγ, confirming the GLP1R signaling pathway-dependent mechanisms. Moreover, Semaglutide and Pioglitazone also attenuated type 2 immune responses and neutrophil influx, both of which are known drivers of mucus hypersecretion, and reduced the P. aeruginosa burden in a chronic bronchitis model of infection in mouse lungs. Our findings identify a promising adjunctive therapeutic avenue for COPD by repurposing FDA-approved Semaglutide and Pioglitazone, which are readily available for clinical use."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Transplantation • MUC5AC

Innate Immune Profile in Diabetes Mellitus Rat Treated with Acalypha Indica Extract: Focus on TLR-2, TLR-4, Nos2, Arg1, and Liver Inflammation. (PubMed, Int J Prev Med) - "Twenty-five Sprague-Dawley rats were divided into five groups: the normal group, high fructose and cholesterol (HFC) group, HFC + Ai 250 mg/kgBW group, HFC + Ai 400 mg/kgBW group and HFC + pioglitazone (Pgz) group...The confidence level used was 95%. Ai extract can reduce RBG and FBG but cannot reduce inflammation in the liver."

Journal • Preclinical • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • ARG1 • NOS2 • TLR2 • TLR4

A flow cytometry-based assay system for the in vitro screening of anti-steatotic compounds. (PubMed, In Vitro Model) - "The assay was validated using known anti-steatotic drugs, where Saroglitazar, Pioglitazone, Empagliflozin, and Atorvastatin significantly reduced lipid accumulation in HepG2 cells. The present flow cytometry assay is a human cell-based and animal-free system that offers a sensitive, accurate, and high-throughput platform for evaluating anti-steatotic compounds, with clear advantages over conventional methods for early-stage drug discovery. The online version contains supplementary material available at https://doi.org/10.1007/s44164-026-00110-4."

Journal • Preclinical • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

Physicochemical interactions between oral drug products: An integrated in vitro and PBPK modeling approach. (PubMed, Int J Pharm) - "This study combined biorelevant in vitro testing and physiologically based pharmacokinetic (PBPK) modeling to investigate such interactions between three commercially available drug products SPORANOX (itraconazole), ACTOS (pioglitazone) and GEVILON (gemfibrozil). This work highlights the potential relevance of physicochemical interactions between different drug products for the efficacy and safety of oral pharmacotherapy. The staged approach presented herein enables early detection of such interactions so that formulation strategies can be applied to mitigate them."

Journal • Preclinical

Serum Vitamin D Levels in Patients with Lichen Planopilaris Before and After Systemic Treatment with Hydroxychloroquine or Pioglitazone (EADV 2026) - No abstract available

Clinical • Lichen Planus

Efficacy and safety of pioglitazone in lichen planopilaris in comparison with hydroxychloroquine: Prospective non-inferiority study (EADV 2026) - No abstract available

Clinical • Head-to-Head • Lichen Planus

Antidiabetic drug exposure and risk of bladder cancer: A systematic review and meta-analysis. (PubMed, Urologia) - "We did not demonstrate a statistically significant association between pioglitazone use and bladder cancer risk. However, several individual studies suggested a possible duration-dependent effect with prolonged exposure. Metformin use was associated with a lower risk of bladder cancer (pooled RR = 0.67, 95% CI 0.46-0.98), although substantial heterogeneity was observed. SGLT2 inhibitors appear oncologically safe with respect to bladder cancer."

Journal • Retrospective data • Bladder Cancer • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus

PHLDA1 as a Key Regulator in Renal Ischemia-Reperfusion Injury: Implications for Fatty Acid Metabolism and Ferroptosis (TTS 2026) - "Genetic interventions included Phlda1 knockout mice, PHLDA1 knockdown/overexpression, and pharmacological modulation using the PPARγ agonist pioglitazone and antagonist GW9662... PHLDA1 aggravates renal IRI by suppressing the PPARγ/CPT1α axis, leading to defective FAO, lipid accumulation, and subsequent ferroptosis. This study identifies PHLDA1 as a novel regulator linking metabolic dysfunction to ferroptotic cell death in renal IRI, offering a promising diagnostic biomarker and therapeutic target for ischemic kidney injury.Figure 1. Renal ischemia-reperfusion injury induces PHLDA1 overexpression and impairs fatty acid β-oxidation.Figure 2."

Cardiovascular • Metabolic Disorders • Renal Disease • Reperfusion Injury • ACSL1 • ACSL4 • FABP4 • GPX4 • PHLDA1

Incremental effects of SGLT2 inhibitors, GLP-1 receptor agonists, and pioglitazone in type 2 diabetes and MASLD across Asian study settings: a systematic review and meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "Comparative safety also remains uncertain because adverse-event reporting was heterogeneous and incomplete. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251231137."

Clinical • Journal • Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Pioglitazone protects against thioacetamide-induced liver fibrosis via AMPK-mediated inhibition of the TGF-β/Smad fibrotic cascade. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "These beneficial effects were associated with increased hepatic p-AMPK expression and reduced oxidative stress, evidenced by decreased malondialdehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) levels and restoration of reduced glutathione (GSH) content, as well as suppression of the transforming growth factor-β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling pathway. PIO mitigates TAA-induced hepatic fibrosis, potentially through AMPK activation and subsequent suppression of the TGF-β/Smad signaling pathway, highlighting its potential as a promising antifibrotic agent."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • AMPK • SMAD4 • TGFB1

From Molecular Mechanisms to Clinical Strategies: A Comprehensive Overview of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). (PubMed, Int J Mol Sci) - "Current management relies primarily on lifestyle modifications, targeted pharmacotherapy (such as pioglitazone, GLP-1 receptor agonists, SGLT-2 inhibitors), and novel experimental therapies. Consequently, MASLD requires a multidisciplinary approach emphasizing early diagnosis, risk stratification, and comprehensive treatment of both hepatic and extrahepatic manifestations."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus

Macrophage-Targeted Cyclodextrin-Based Metal-Organic Frameworks Restore Redox-Efferocytosis Coupling to Promote Osteochondral Repair in Temporomandibular Joint Osteoarthritis. (PubMed, Adv Healthc Mater) - "To correct this mismatch, this study develops MCP@CD-MOF, a macrophage-targeting cyclodextrin metal-organic framework nanoplatform co-loaded with curcumin and pioglitazone...Mechanistically, MCP@CD-MOF coordinates the FOXO1-GPX4/ERK1/2-NOX2 redox network with the FAK-DOCK1-PAK1 efferocytosis pathway. Collectively, MCP@CD-MOF integrates redox regulation with efferocytosis-driven macrophage reprogramming, providing a disease-modifying biomaterial strategy that couples inflammation resolution with osteochondral repair in TMJOA."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • DOCK1 • GPX4

Therapeutic Potential of Pioglitazone-Augmented Indocyanine Green-Driven Photodynamic Therapy in Papillary Thyroid Cancer: An In Vitro Study. (PubMed, Photobiomodul Photomed Laser Surg) - "These findings demonstrate that PIO potentiates the antitumor activity of ICG-PDT by inducing oxidative stress and mitochondrial dysfunction. This in vitro approach suggests a rational, combinatorial strategy that merits further investigation in preclinical models of thyroid cancer."

Journal • Preclinical • Metabolic Disorders • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Tetramethylpyrazine ameliorates metabolic dysfunction-associated steatohepatitis by modulating gut microbiota dysbiosis and restoring intestinal barrier integrity. (PubMed, Br J Pharmacol) - "TMP exerts protective effects against MCD diet-induced MASH by improving hepatic pathology and restoring gut-liver axis homeostasis, including intestinal barrier integrity, gut microbiota composition, BA and SCFA metabolism and faecal metabolic balance."

Journal • Fibrosis • Hepatitis B • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Transplantation • CLDN1 • IL1B • IL6 • OCLN • TJP1 • TNFA

Comparative Efficacy of Promising Targets in the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Network Meta-analysis. (PubMed, J Clin Transl Hepatol) - "Incretin-based co-agonists and FGF21 analogs showed favorable profiles across key endpoints, while d-(R)-pioglitazone and GLP-1/GIP dual RAs ranked higher for fibrosis improvement and steatohepatitis resolution, respectively. SUCRA rankings should be interpreted in conjunction with effect sizes, uncertainty, and available safety data."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21 • GCG

Insight Into the Recent Advancements in Thiazolidinedione Derivatives as PPAR-γ Agonists for the Treatment of Type 2 Diabetes. (PubMed, Mini Rev Med Chem) - "The potential of thiazolidinediones, regarding their chemical development and interaction with PPAR-γ receptors, is well known. Newer TZD analogues that offer enhanced safety and tolerability are anticipated to become widely accessible soon."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Bcl-xL Promotes Gastric Tumorigenesis via Apoptosis-Independent Wnt/β-Catenin Activation and PPARγ Suppression. (PubMed, Cell Mol Gastroenterol Hepatol) - "Bcl-xL promotes gastric tumorigenesis through dual mechanisms-enhancing Wnt signaling and suppressing PPARγ-and highlight Bcl-xL as a potential therapeutic target while suggesting PPARγ activation may be protective."

Journal • Diabetes • Gastric Cancer • Metabolic Disorders • Oncology • Solid Tumor • BCL2L1 • HNF1A • PPARG

Efficacy of pioglitazone in correcting ovulatory functions among polycystic ovary syndrome patients. (PubMed, Bioinformation) - "After six months of treatment, 72.6% of patients achieved restored ovulation with improved hormonal profiles. Pioglitazone thus emerges as an effective alternative to metformin, improving menstrual cycles, ovulation, hyperandrogenism, and reducing the risk of type 2 diabetes."

Journal • Diabetes • Infertility • Metabolic Disorders • Polyendocrine Metabolic Ovarian Syndrome • Sexual Disorders • Type 2 Diabetes Mellitus

GLP-1 receptor agonist and pioglitazone combination therapy and risks of mortality and advanced liver outcomes in patients with type 2 diabetes (EASD 2026) - "In patients with T2D without viral hepatitis or alcohol-related liver disease, combined GLP-1 RA and pioglitazone therapy was associated with lower cardiovascular and all-cause mortality but not with reduced risks of advanced liver outcomes. These findings suggest that the principal benefit of this combination may lie in systemic survival advantages rather than prevention of liver disease progression. Prospective studies are needed to confirm these observations."

Clinical • Combination therapy • Metastases • Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Prevalence of liver fibrosis in patients with early type 2 diabetes and MASLD (EASD 2026) - "The subgroups with SD and LD were not different for sex distribution, BMI and waist circumference but LD were older, with higher prevalence of CVD and CKD and more frequently on GLP1- RAs, Pioglitazone, SGLT2-i and basal insulin treatments and with more intensive lipid and blood pressure lowering therapies... In conclusion, among patients with MASLD and T2DM, at least 1 out of 3 individuals had LSM>8 KPa and the prevalence of liver fibrosis and the proportion of patients with more severe organ damage were not different between those with short in comparison with long duration of T2DM. These data show that in patients with MASLD, liver fibrosis is largely prevalent early in the natural history of the disease suggesting that the screening for this condition should be performed at the onset of the disease."

Clinical • Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Anular y castigar: Terapias de conversión como actos de tortura en América Latina. (PubMed, Torture) - "Además, se argumenta que estas prácticas deben ser comprendidas como dispositivos estructurales de violencia que operan bajo lógicas culturales y sociales de subordinación. Finalmente, se propone una ruta de acreditación jurídica y forense, basada en la identificación del propósito teleológico y la implicación directa o indirecta del Estado."

Journal

PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice. (PubMed, CNS Neurosci Ther) - "Pioglitazone alleviates sepsis-induced brain dysfunction and improves survival in mice in a PPAR-γ-dependent manner."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Mood Disorders • Psychiatry • Septic Shock • CLDN5 • IL10 • IL1B • IL6 • PPARG • TLR4 • TNFA