Genes and Health GIPR Study

Obesity and diabetes are an increasing global health challenge, especially for South Asian communities. There have been significant recent advances in treatment through the development of injectable treatments for obesity and diabetes. One of the most effective drugs currently available (tirzepatide/Mounjaro) works by mimicking (activating) two hormone systems – GLP-1 and GIP – leading to weight loss of around 20% body weight through reduced appetite.

Activating the GIP system is important for this additional benefit over previous drugs that only used the GLP-1 system. However, it’s not clear exactly how this works since studies in humans and mice suggest that losing the response to GIP (“loss of function”) also leads to weight loss. There is now a drug being developed that blocks rather than activates the GIP receptor (GIPR).

To understand how activating and blocking the GIP system both cause weight loss and to understand the GIP system better in general, we have assessed 4 participants from the Genes and Health study who carry a very rare genetic change which means they do not have functioning receptors for GIP. One key finding was that they have unusually high levels of another hormone which is known to reduce appetite and weight.

We are aware of two participants in Born in Bradford whose DNA sequencing suggests they also do not have functioning receptors for GIP. We would like to invite them to take part in the Genes and Health study for a medical history, brief examination (such as height and weight) and fasting blood tests. This would allow us to see if the hormone changes we found in the participants we have already seen are consistent across more people with the same gene changes.

If so, this could be an important discovery that helps us understand how impairment of GIPR leads to weight loss and could help form the basis for new treatments for obesity and diabetes in the future.