FGF19

Where it comes from

Made in

Enterocytes of the ileum, when bile acids activate the receptor FXR

Sent out by

An hour or two after a meal, when bile acids reach the ileum; also from the gallbladder lining

Acts on

• Liver (bile acid synthesis, glycogen, protein synthesis)
• Gallbladder (filling)
• Hypothalamus

What it does

• Shuts off bile acid synthesis (CYP7A1) in the liver, the loop worked out in mice lacking the hormone ¹
• Fills the gallbladder between meals
• Lowers glucose and raises energy use in mice without the growth effect of insulin

In medicine

• Low FGF19 is one cause of bile acid diarrhoea, a research finding with a possible test behind it ²
• No approved medicine. The natural hormone is given to nobody, because FGF19 drives liver tumours in mice, so every analogue has had to be engineered around that

Beyond the body’s own use

• Aldafermin, an engineered FGF19 built not to drive liver tumours, lowered liver fat in earlier work, but in a 171-patient phase 2b trial its fibrosis endpoint was no better than placebo and the fatty liver programme stopped ³
• In primary sclerosing cholangitis it cut bile acid synthesis sharply and improved fibrosis markers, but left alkaline phosphatase, the endpoint it was judged on, unchanged; a planned trial was withdrawn in 2024 ⁴
• Nothing containing FGF19 is approved and it is not taken outside medicine. The narrower question is whether an engineered FGF19 helps bile acid diarrhoea, where the hormone is what is actually missing ²