Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the most prevalent chronic liver condition worldwide, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and may progress to cirrhosis or hepatocellular carcinoma [1,2]. Importantly, emerging evidence demonstrates that hepatic fibrosis, rather than steatosis alone, dictates the natural course of MASLD and serves as both a predictor of liver-related outcomes and an important indicator of systemic health and cardiovascular risk [3,4].

The prevalence of MASLD is particularly high among individuals with type 2 diabetes (T2D). Approximately 50–70 % of T2D patients have MASLD, a phenomenon closely associated with insulin resistance, metabolic syndrome, and obesity [5,6]. Beyond its direct hepatic consequences, MASLD significantly increases the risk of adverse cardiovascular outcomes, renal dysfunction, and all-cause mortality [7]. Therefore, therapeutic strategies that simultaneously address glycemic control and liver health in T2D patients represent an important clinical challenge.

Nuclear receptors are ligand-activated transcription factors that serve as master regulators of hepatic metabolism, inflammation, and fibrogenesis, with their dysregulation being heavily implicated in the pathogenesis and progression of MASLD [8,9]. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate critical metabolic pathways, with three distinct isoforms—PPARα, PPARγ, and PPARδ—each controlling specific processes essential for metabolic homeostasis [[10], [11], [12]]. First-generation PPAR agonists, primarily thiazolidinediones targeting PPARγ, effectively alleviated hepatic steatosis as demonstrated by pioglitazone's ability to reduce liver fat content [13,14]. However, their clinical utility has been limited by adverse effects including weight gain and fluid retention, prompting the development of next-generation dual and pan-PPAR agonists with balanced activation profiles [15]. Recent clinical trials of saroglitazar (dual PPARα/γ agonist) and lanifibranor (pan-PPAR agonist) have shown promising results in MASLD patients, suggesting that balanced activation of multiple PPAR isoforms may provide comprehensive metabolic benefits with fewer side effects [16,17].

Chiglitazar is an innovative pan-PPAR agonist that simultaneously engages all three PPAR subtypes with a balanced activation profile [18]. Clinical investigations have established chiglitazar's efficacy in improving glycemic control and lipid profiles in T2D patients [[19], [20]]. Preclinical models further suggest that chiglitazar can ameliorate hepatic steatosis through enhanced fatty acid oxidation, reduced lipogenesis, and attenuated inflammatory signaling [21]. Despite these promising findings, there remains a significant knowledge gap regarding chiglitazar's effects on MASLD in clinical settings, particularly in T2D patients.

The aim of this prospective real-world study was to evaluate the impact of chiglitazar on hepatic steatosis and fibrosis parameters in T2D patients with MASLD, as measured by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). By investigating the effects of this pan-PPAR agonist on both liver health and metabolic parameters, we sought to determine whether chiglitazar represents a potential therapeutic option that can simultaneously address the interlinked pathophysiology of T2D and MASLD.