MASH / NAFLD

In the phase 3 ESSENCE trial, once-weekly semaglutide 2.4 mg resolved steatohepatitis without worsening fibrosis in 62.9% vs 34.3% placebo and reduced fibrosis in 36.8% vs 22.4% at week 72.

In a phase 2 trial, survodutide improved MASH without worsening fibrosis in up to 62% vs 14% placebo and reduced liver fat by >=30% in up to 67% vs 14% at 48 weeks.

In the phase 2 SYNERGY-NASH trial, tirzepatide resolved MASH without worsening fibrosis in 44-62% of patients (5-15 mg) vs 10% placebo at 52 weeks.

In a phase 2a MASLD substudy, retatrutide reduced liver fat by 81-82% at higher doses (8-12 mg) vs +0.3% placebo at 24 weeks, with normal liver fat achieved in up to 86%.

In a randomized trial in people with HIV and NAFLD, tesamorelin 2 mg daily reduced hepatic fat fraction by a relative 37% vs placebo over 12 months.

In a high-fat-diet mouse model and hepatocyte model, mazdutide reduced hepatic steatosis, liver injury markers and inflammation via PERK/ER-stress and NF-kB modulation.

In a 52-week RCT in non-diabetic MASLD, empagliflozin 10 mg reduced MRI-PDFF liver fat more than placebo (-2.49% vs -1.43%), with greater weight and waist reduction.