MGAT2 inhibitor decreases liver fibrosis and inflammation in murine NASH models and reduces body weight in human adults with obesity

Cell Metab. 2022 Nov 1;34(11):1732-1748.e5. doi: 10.1016/j.cmet.2022.10.007.


Monoacylglycerol acyltransferase 2 (MGAT2) is an important enzyme highly expressed in the human small intestine and liver for the regulation of triglyceride absorption and homeostasis. We report that treatment with BMS-963272, a potent and selective MGAT2 inhibitor, decreased inflammation and fibrosis in CDAHFD and STAM, two murine nonalcoholic steatohepatitis (NASH) models. In high-fat-diet-treated cynomolgus monkeys, in contrast to a selective diacylglycerol acyltransferase 1 (DGAT1) inhibitor, BMS-963272 did not cause diarrhea. In a Phase 1 multiple-dose trial of healthy human adults with obesity (NCT04116632), BMS-963272 was safe and well tolerated with no treatment discontinuations due to adverse events. Consistent with the findings in rodent models, BMS-963272 elevated plasma long-chain dicarboxylic acid, indicating robust pharmacodynamic biomarker modulation; increased gut hormones GLP-1 and PYY; and decreased body weight in human subjects. These data suggest MGAT2 inhibition is a promising therapeutic opportunity for NASH, a disease with high unmet medical needs.

Keywords: DCA; DGAT; GLP-1; MGAT2; NAFLD; NASH; PYY; dicarboxylic acid; liver fibrosis; steatosis; weight loss.

MeSH terms

  • Adult
  • Animals
  • Body Weight
  • Clinical Trials, Phase I as Topic
  • Humans
  • Inflammation / drug therapy
  • Liver Cirrhosis / drug therapy
  • Mice
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Obesity* / drug therapy


  • 2-acylglycerol O-acyltransferase