Cusi K, Alkhouri N, Harrison SA, et al. - According to this randomized, double-blind, placebo-controlled phase 2a study (STAMP-NAFLD), when compared with placebo, PXL770 therapy did not achieve the primary endpoint of improved liver fat. The therapy was well tolerated. Given the evidence that PXL770 treatment improved metabolic characteristics, AMPK activation could be a promising pharmaceutical target for patients with type 2 diabetes and NAFLD, and it could also be considered for future evaluation in patients with non-alcoholic steatohepatitis.

• Three hundred eighty-seven patients were screened between March 29, 2019, and March 13, 2020, with 120 of them included in the modified intention-to-treat and safety analyses (30 in the 250 mg once daily group, 30 in the 250 mg twice daily group, 29 in the 500 mg once daily group, and 31 in the placebo group).

• At week 12, the mean relative change from baseline in liver fat content was −1·1% in the placebo group, −1·0% in the 250 mg once daily group, −14·3% in the 250 mg twice daily group, and −14·7% in the 500 mg once daily group.

• There was at least one treatment-emergent adverse event in 23 (77%) of 30 patients in the 250 mg once daily group, 20 (67%) of 30 patients in the 250 mg twice daily group, 21 (72%) of 29 patients in the 500 mg once daily group, and 21 (68%) of 31 patients in the placebo group.

• Diarrhea was the most common treatment-emergent adverse event.

• There were no life-threatening incidents or treatment-related deaths.