ReviewJournal of cardiovascular pharmacology2020
The Glitazars Paradox: Cardiotoxicity of the Metabolically Beneficial Dual PPARα and PPARγ Activation.
Review in Journal of cardiovascular pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.Scientific reports · 2024 · on this mapPooled it
- Current Drug Development Pipeline for MASLD and MASH: Focusing on Cardiovascular Comorbidities.Biomedicines · 2026Review
- Therapeutic Trends in Diabetes Management: A Review on Oral Hypoglycemic Agents (OHAs) Utilization in Tertiary Care.Cardiovascular & hematological disorders drug targets · 2026Review
- Suppression of adipocyte ABHD6 favors anti-inflammatory and adipogenic programs to preserve adipose tissue fitness in obesity.Molecular metabolism · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Nanomedicine targeting PPAR in adipose tissue macrophages improves lipid metabolism and obesity-induced metabolic dysfunction.Science advances · 2025Article
- Deletion of PTP1B in cardiomyocytes alters cardiac metabolic signaling to protect against cardiomyopathy induced by a high-fat diet.Science signaling · 2025Article
- The Many Facets of PPAR-γ Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions.Current obesity reports · 2025Review
- Cardioprotection strategies for anthracycline cardiotoxicity.Basic research in cardiology · 2025Review
- Triterpenoids from Chios Mastiha Resin Against MASLD-A Molecular Docking Survey.Current issues in molecular biology · 2025Article
- Novel Therapeutics for Type 2 Diabetes Mellitus-A Look at the Past Decade and a Glimpse into the Future.Biomedicines · 2024Review
- Futile lipid cycling: from biochemistry to physiology.Nature metabolism · 2024Review
- Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy.Pharmaceutics · 2023Review
- Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome.Current issues in molecular biology · 2023Article
- Prediction of drug-induced liver injury and cardiotoxicity using chemical structure and in vitro assay data.Toxicology and applied pharmacology · 2022Article
- In vitro activity of a panel of per- and polyfluoroalkyl substances (PFAS), fatty acids, and pharmaceuticals in peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma, and estrogen receptor assays.Toxicology and applied pharmacology · 2022Article
- Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate.International journal of molecular sciences · 2022Article
- Structural Basis for PPARs Activation by The Dual PPARα/γ Agonist Sanguinarine: A Unique Mode of Ligand Recognition.Molecules (Basel, Switzerland) · 2021Article
- Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The most common complications in patients with type-2 diabetes are hyperglycemia and hyperlipidemia that can lead to cardiovascular disease. Alleviation of these complications constitutes the major therapeutic approach for the treatment of diabetes mellitus. Agonists of peroxisome proliferator-activated receptor (PPAR) alpha and PPARγ are used for the treatment of hyperlipidemia and hyperglycemia, respectively. PPARs belong to the nuclear receptors superfamily and regulate fatty acid metabolism. PPARα ligands, such as fibrates, reduce circulating triglyceride levels, and PPARγ agonists, such as thiazolidinediones, improve insulin sensitivity. Dual-PPARα/γ agonists (glitazars) were developed to combine the beneficial effects of PPARα and PPARγ agonism. Although they improved metabolic parameters, they paradoxically aggravated congestive heart failure in patients with type-2 diabetes via mechanisms that remain elusive. Many of the glitazars, such as muraglitazar, tesaglitazar, and aleglitazar, were abandoned in phase-III clinical trials. The objective of this review article pertains to the understanding of how combined PPARα and PPARγ activation, which successfully targets the major complications of diabetes, causes cardiac dysfunction. Furthermore, it aims to suggest interventions that will maintain the beneficial effects of dual PPARα/γ agonism and alleviate adverse cardiac outcomes in diabetes.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.