Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD.

Summary

In a randomized, placebo-controlled phase II trial (n=38), lanifibranor reduced intrahepatic triglycerides by ~44–50% versus 12–16% with placebo, with 65–79% achieving ≥30% IHTG reduction and 25% steatosis resolution. Hepatic and peripheral insulin sensitivity improved, adiponectin rose 2.4-fold, and cardiometabolic markers improved, with modest weight gain (+2.7%) and mild adverse events.

Key Findings

• Lanifibranor reduced intrahepatic triglyceride content by ~44–50% vs. 12–16% with placebo; steatosis resolution occurred in 25% vs. 0%.
• Improved hepatic and peripheral insulin sensitivity (reduced endogenous glucose production and increased insulin-stimulated Rd); adiponectin increased 2.4-fold.
• Secondary metabolic markers improved (fasting glucose, insulin, HOMA-IR, HbA1c, HDL-C); modest weight gain (+2.7%) and mild AEs observed.

Clinical Implications

Lanifibranor may offer a pharmacologic option to target insulin resistance and steatosis beyond weight loss strategies in T2D with MASLD; monitoring for weight gain and hematologic changes is warranted.

Limitations

• Single-center, small sample size (n=38) with 24-week follow-up limits generalizability and long-term inference
• Weight gain and hemoglobin decrease warrant longer-term safety evaluation

Future Directions

Larger, multicenter phase III trials assessing histologic NASH/MASH endpoints, cardiovascular/renal outcomes, and combination strategies with weight-loss agents.