Nature Reviews Endocrinology | 2021
Phase IIa results for potential NAFLD therapy
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by increased hepatic de novo lipogenesis, which leads to accumulation of triglycerides in the liver. ACC catalyses an early step in de novo lipogenesis, leading researchers to develop a novel ACC1/2 inhibitor. Two parallel phase IIa trials have now tested this inhibitor; one as a monotherapy and one in combination with a DGAT2 inhibitor. The monotherapy resulted in dosedependent reductions in liver fat content and improvements in some biomarkers of nonalcoholic steaotohepatitis. However, the monotherapy also resulted in an increase in serum levels of triglycerides, which suggests it could have an adverse cardiometabolic profile. These effects were mitigated with the combination therapy. The authors suggest that the combination therapy would be an effective way of addressing the limitations of ACC inhibitor monotherapy.