Type 2 diabetes affects millions of people around the world, and a new international study co-led by the University of Adelaide, Oxford University, ETH Zurich and Stanford University has found that one in 10 people may not be benefiting from common drugs used to treat the condition.
The collaboration found that a genetic variation, present in 10 percent of the population, can prevent GLP-1 receptor treatments such as Ozempic from working effectively.
This result highlights the need for a more individualized approach to prescribing these widely used drugs, which are also used for weight loss.
“In recent years, the treatment of diabetes and obesity has greatly improved with the widespread use of GLP-1-based drugs such as Ozempic. However, not all patients respond well to these treatments.” Lead author Dr Mahesh Umapathysivam from the Center for Excellence at the University of Adelaide said: Transforming nutritional science into health.
“Understanding why and how to predict who will respond well and who will respond poorly gives us the best chance of getting the right drug to the right patient.”
The survey results were published in a magazine genomic medicinewere the results of multiple human and animal studies that investigated why two specific genetic mutations within the PAM gene increase the risk of type 2 diabetes.
It builds on previous research that showed: pam This gene increases the risk of type 2 diabetes by reducing the amount of insulin released by the pancreas and changing the structure of hormones such as the GLP-1 hormone, which regulates blood sugar.
In this latest study, researchers pam This gene decreased the effectiveness of the enzyme and increased natural GLP-1 levels while blocking the hormone’s beneficial effects on blood sugar levels. This suggests that people with PAM mutations had some degree of resistance to GLP-1.
Researchers looked at how this affected the body’s response to GLP-1 drugs. In people with the PAM gene mutation, the drug’s hypoglycemic effect was reduced by up to 44 percent after six months of use.
Only 11 percent of carriers of the more harmful PAM variant achieved recommended blood sugar levels while taking this type of drug, compared with about 25 percent of people without the gene variant.
Our study is one of the first to provide detailed clinical evidence showing how people with certain genetic mutations are at increased risk of developing diabetes and have a reduced response to GLP-1 receptor drugs. ”
Dr Mahesh Umapathishivam, University of Adelaide Center for Research Excellence: Transforming Nutrition Science into Health Study Lead Author
“As this research develops, other genetic variants have been discovered that predict response to diabetes drugs, so this information could be combined to determine which diabetes drugs improve blood sugar levels and are most effective in a patient’s diabetes care.”
GLP-1-based drugs like Ozempic are often injectable treatments that manage blood sugar levels by stimulating the pancreas to produce insulin and controlling appetite.
“Type 2 diabetes is a leading cause of morbidity and mortality worldwide. Despite the availability of multiple hypoglycemic agents, only half of people with diabetes achieve recommended blood sugar targets.” Dr. Umapathy Shivam said.
“This shows that although there have been significant improvements in treatments, we need to improve the care we provide to patients, and this may be achieved through a more personalized approach to prescribing these widely used drugs.”
This ongoing research effort is supported by funding from Diabetes Australia.
“Our hope is that this study will provide a blueprint for future studies examining genetic mutations, ultimately leading to the development of genetic test panels that identify the best drugs for patients, maximizing the likelihood of successful diabetes treatment and minimizing the risk of adverse outcomes.” Dr. Umapathy Shivam said.
