GDF15

Where it comes from

Made in

Nearly any cell under stress; the placenta in large amounts; the prostate; many tumours

Sent out by

Cell stress, inflammation, exercise, pregnancy, and the drug metformin, which raises it from the gut

Acts on

• Brainstem (nausea, food aversion, less eating)
• Through the brain, fat and muscle

What it does

• Causes nausea and loss of appetite when the body is sick, pregnant or poisoned; it has one receptor, in one small part of the brainstem, and nothing else responds to it ¹
• Drives the weight loss of cancer cachexia
• Rises with age and predicts death in heart disease and in older people generally

In medicine

• A research prognostic marker in heart failure, cancer and ageing
• Ponsegromab, an antibody against GDF15, increased weight (by 1 to 3 kg more than placebo over 12 weeks) and improved appetite in cancer cachexia in a phase 2 trial; a phase 2/3 trial in pancreatic cancer began in 2025 ²
• Variation in GDF15 and its receptor explains part of the risk of hyperemesis gravidarum, the severe vomiting of pregnancy ³

Beyond the body’s own use

• GDF15 analogues were tried for obesity, since the hormone suppresses appetite; the one that reached phase 2 produced little weight loss and was dropped in 2023
• Metformin raises GDF15 in people, and in mice metformin’s effect on weight depends on it, which makes the hormone part of how the oldest diabetes drug works ⁴
• Read together the evidence runs one way: blocking GDF15 helps people who are wasting more than giving it helps people who are heavy ²