Tirzepatide, the blockbuster GLP/GIP weight-loss drug marketed as Zepbound, was recently compared to placebo in patients with NASH, also known as metabolic dysfunction–associated steatohepatitis or fatty liver disease. The SYNERGY-NASH trial randomized 190 patients with NASH and F2 or F3 fibrosis to three doses of tirzepatide - 5 mg, 10 mg, and
15 mg - or placebo. After 52 weeks, NASH resolution occurred in 44%, 56%, 62%, and 10%, respectively, while a decrease in fibrosis stage of ≥ 1 was seen in 55%, 51%, 51%, and 30% (all tirzepatide-placebo comparisons were significant). Tirzepatide-treated patients lost 11 - 16% of their body weight, depending on the dose. Drug discontinuations due to side effects were rare in all groups (≤4%).
NASH is driven by hepatocellular adiposity, so it is not surprising that tirzepatide-induced weight loss improved liver pathology. In a previous trial, semaglutide was significantly better than placebo for NASH resolution but not fibrosis improvement. [
PMID 33185364]
Resmetirom is the only medication currently FDA-approved to treat NASH, and while results from different studies are not comparable linearly, nothing in resmetirom's pivotal trial suggests that it is superior to tirzepatide. Furthermore, it does not cause weight loss, giving it no benefit in other obesity-related conditions.