Long-term pioglitazone use in MASLD patients: insights from a multicentric preliminary study

Abstract

Background and aims: This multi-center retrospective study evaluated the long-term effects of pioglitazone therapy on liver stiffness, hepatic steatosis, and other non-invasive biomarkers in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Methods: A total of 65 patients from three Brazilian public hospitals treated with pioglitazone at doses of 30‒45 mg/day up to 10-years were retrospectively analyzed. Hepatic parameters, including Vibration-Controlled Transient Elastography (VCTE), Controlled Attenuation Parameter (CAP), and FibroScan-AST score, were evaluated before and after treatment. Patients were stratified into two groups based on treatment duration: 1‒3 years and 4‒10 years.

Results: Significant reductions in Alanine Aminotransferase (ALT) and Gamma-Glutamyl Transferase (GGT) levels were observed in both treatment groups, indicating improvement in liver enzyme profiles. A significant decrease in CAP levels was observed only in the 4‒10 year group (p = 0.002), suggesting a reduction in liver steatosis. Improvement in FAST™ scores was observed in both groups (1‒3 years, p = 0.042; 4‒10 years, p = 0.012). In logistic regression analysis, dyslipidemia was associated with a non-significant trend toward higher odds of liver stiffness reduction (adjusted OR = 1.92, 95 % CI 0.58‒6.45, p = 0.284).

Conclusions: These findings highlight both the metabolic and hepatic benefits of long-term pioglitazone therapy. They reinforce its potential as a cost-effective and accessible treatment option for MASLD, particularly in resource-limited settings where newer therapeutic alternatives are unavailable.

Keywords: MASH; MASLD; Pioglitazone.

Fig. 1

Flow diagram.

Fig. 2

Parameters affected by Pioglitazone use. A and B show the FAST™ score at baseline and over time (A: 1–3 years, B: 4–10 years), with significant reductions indicated (*p < 0.05). C and D display Liver Stiffness (kPa), showing no significant changes over time (ns = not significant). Panels E and F represent Controlled Attenuation Parameter (CAP), reflecting liver fat levels. While panel E (1–3 years) shows no significant difference, panel F (4–10 years) shows a significant reduction (**p < 0.01). G and H illustrate Alanine Aminotransferase (ALT) levels, with significant reductions observed in both timeframes (*p < 0.05). Panels I and J show HbA1c ( %) changes, with no significant change in the 1–3 years group (I) but a significant reduction (*p < 0.05) in the 4–10 years group (J).

Fig. 3

Logistic regression – LSM reduction. SAH, Systemic Arterial Hypertension; T2DM, Type 2 Diabetes Mellitus; DLD, Dyslipidemia; BMI, Body Mass Index.