A new pre-print by LCDS researchers Robert Campbell and Melinda Mills investigates the potential health side effects of drugs that target the GLP-1 receptor, a class of medications increasingly used to treat diabetes and obesity.
GLP-1R drugs have seen rapid global uptake in recent years, raising hopes for tackling obesity and related diseases. At the same time, their expanding use has intensified calls for better evidence on possible unintended consequences for population health — particularly as oral formulations are developed and access broadens further.
Using genetic data from the UK Biobank, the study applies a large-scale “phenome-wide” approach to examine how variation in GLP1R gene expression is linked to nearly 400 diseases. This method allows the researchers to assess likely long-term effects of GLP-1R drugs by exploiting naturally occurring genetic differences in the population.
The authors identify 92 significant associations between GLP1R expression and disease risk, including 58 protective and 34 adverse effects. Higher GLP1R expression is linked to reduced risks for several major conditions, including cardiovascular, kidney, and metabolic diseases. At the same time, it is associated with increased risks for some musculoskeletal conditions, vitamin D deficiency, and, most notably, a range of maternal and neonatal health outcomes.
The findings raise particular concerns for women who may become pregnant. The study suggests that higher GLP1R activity can be linked to elevated risks for complications affecting pregnancy and newborn health, highlighting the importance of careful monitoring as these drugs become more widely used.
Robert Campbell, lead author of the study, commented: “GLP-1 drugs are transforming the treatment of obesity and diabetes, but their rapid uptake means we urgently need a clearer picture of their broader health effects. By using genetic data from half a million people, we can begin to anticipate both the benefits and the risks at the population level.”
Professor Melinda Mills, co-author of the study, adds: “We now have the increased widespread take-up of GLP-1 drugs and potential growth due to oral pills. This means a larger population will be using these drugs. Given that some women are unaware they are pregnant and the longer life of these drugs in the body, our study underscores the potentially dangerous side effects for pregnant women and neonates.”
The study also examines a second drug target, CETP, finding that its effects are largely confined to cardiovascular disease, in contrast to the wide-ranging impacts observed for GLP1R. This comparison illustrates how genetic evidence can help distinguish between drug targets with high potential for both benefit and risk.
The pre-print can be found here: https://www.medrxiv.org/content/10.64898/2026.01.24.26344404v2
