DGAT1 inhibitors + DGAT2 inhibitors

DGAT1 inhibitors + DGAT2 inhibitors refers to the pharmacological combination of agents that inhibit both diacylglycerol O-acyltransferase 1 (DGAT1) and diacylglycerol O-acyltransferase 2 (DGAT2), the two key enzymes catalyzing the final step in triglyceride (TG) synthesis by converting diacylglycerol and fatty acids into triglycerides in mammalian tissues. Inhibition of both DGAT1 and DGAT2 results in a synergistic reduction of triglyceride synthesis and depot, impacting metabolic processes in hepatocytes, cardiac cells, and potentially tumor cells. This dual inhibition has shown greater efficacy than single enzyme inhibition in preclinical models by reducing hepatic steatosis, improving cellular bioenergetics, lessening fibrogenic activation in hepatic stellate cells, and counteracting extracellular matrix deposition, making it a promising approach for diseases like metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)[5][6]. The main DGAT1 inhibitors used in studies include PF-04620110 and T863, while PF-06424439 is a key DGAT2 inhibitor[7]. Developers of individual inhibitors include Pfizer, AstraZeneca, Abbott, and Novartis, but there is no uniquely approved pharmaceutical product that combines both classes to date.

Other names

DGAT1 and DGAT2 inhibitorsDGAT-1 and DGAT2 inhibitorsDGAT 1 and DGAT2 inhibitorsiDGAT1/2