Table 2 Major clinical trials assessing lipogenesis inhibitors in patients with MASLD

ACC inhibitor

GS-0976

10 patients with NASH and 10 healthy volunteers

Reduce hepatic DNL by 22%, MRI-PDFF LFC by 6.6%, MRE liver stiffness by 0.3Kpa, serum ALT by 44U/L after 12 weeks. Decrease MRI-PDFF liver lipid accumulation more than 30% in 70% of participants

[69]

126 patients with more than 8% of LFC by MRI-PDFF and more than 2.5 kPa of stiffness by MRE or biopsy-proven NASH and F1-F3 fibrosis

Decrease MRI-PDFF LFC by more than 30% in 23–48% participants in a dose-dependent mode after 12 weeks. Increase serum TG in 11–13% of participants

[70]

PF05221304

305 overweight/obese patients with NAFLD (more than 8% LFC by MRI-PDFF) and with more than 2 of 5 risk factors of NAFLD

Reduce MRI-PDFF LFC by 50–65% with PF-05221304 dose ≥ 10 mg QD after 16 weeks

[83]

FAS inhibitor

Denifanstat (TVB-2640)

12 obese men with certain metabolic abnormalities

Reduce fasting DNL by up to 90%, and ALT by 15.8% after 10 days

[73]

99 patients with more than 8% LFC by MRI-PDFF and liver fibrosis of more than 2.5 kPa by MRE or liver biopsy

Reduce LFC by 9.6% in 25 mg group and 28.1% in 50 mg group after 12 weeks

[74]

SCD1 inhibitor

Aramchol

247 patients with NASH proved by biopsy results

Achieve NASH resolution in 16.7% of participants and fibrosis improvement without worsening NASH in 29.5% after 52-week treatment. Reduce ALT by 29.1U/L. Liver fat by MRS was not significantly reduced

[77]

50 patients with HIV-associated NAFLD (more than 5% LFC by MRI-PDFF)

Do not reduce MRI-PDFF LFC or stiffness by MRE and VCTE after 12 weeks

[78]

DGAT2 inhibitor

PF-06427878

24 healthy participants in NCT02855177 and 39 healthy participants in NCT 02391623

Reduce MRI-PDFF LFC and serum ALT, AST, alkaline phosphatase and total bilirubin in healthy adults after 14 days

[80]

IONIS-DGAT2_Rx

44 patients with BMI of 27-39 kg/m², HbA1c of 7.3–9.5% and LFC by MRI-PDFF ≥ 10%

Reduce 5.2% LFC by MRI-PDFF after 13-week treatment

[81]

ACC/DGAT2 inhibitor

PF-05221304 and PF-06865571

99 overweight patients with metabolic syndrome and/or T2DM and more than 5% LFC by MRI-PDFF

Reduce 44.6% LFC by MRI-PDFF and serum TG after 6 weeks

[83]