Incretin-based therapies and PPARγ agonists as regulators of adipokines-Nrf2 axis in diabetic cardiovascular disease

Abstract

Oxidative stress and adipokine imbalance are important contributors to the pathogenesis of diabetic cardiovascular disease. The nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant defense, while adipokines link metabolism and inflammation. Incretin-based therapies and PPARγ agonists may join on these pathways to provide cardiovascular protection beyond glycemic control. This review aims to investigate the current evidence on how incretin-based agents and PPARγ agonists regulate the adipokine-Nrf2 axis and their impact on cardiovascular outcomes in diabetes. A literature search was performed using PubMed, Google Scholar and Scopus to include reviews, experimental, clinical, and translational studies published in English until November 2025. Evidence indicates that incretin-based agents and PPARγ agonists synergistically activate Nrf2 and inhibit NF-kB signaling, leading to improved oxidative status and favorable adipokine levels. Increased adiponectin and omentin, and suppressed resistin, leptin and TNF-α contribute to reduced inflammation and enhanced vascular and myocardial protection. Collectively, combined activation of incretin and PPARγ pathways modulates the adipokine-Nrf2 axis, offering joined antioxidant and anti-inflammatory benefits that may reduce diabetic cardiovascular risk.