Exploring the Potential Effect of GLP1R Agonism on Common Aging-Related Diseases via Glucose Reduction: A Mendelian Randomization Study.

BACKGROUND

Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in managing type 2 diabetes mellitus and weight control. Their potential in treating aging-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed.

METHODS

Using a genetic variant in the GLP1R gene to model the long-term effects of GLP1RAs, this Mendelian randomization (MR) study systematically explored potential causal associations between GLP1R agonism and 12 aging-related diseases and indicators. Genetic summary data sets used in this study were obtained from previous genome-wide association studies.

RESULTS

The primary MR analysis results suggested that GLP1R agonism was potentially positively causally associated with appendicular lean mass (Beta = 0.246, 95% confidence interval [CI] = 0.096-0.396), whole-body fat-free mass (Beta = 0.202, 95% CI = 0.048-0.355), and lung function (forced vital capacity [FVC]; Beta = 0.179, 95% CI = 0.152-0.205; p < .05). Additionally, a potential negative causal association was observed with myocardial infarction (odds ratio = 0.430, 95% CI = 0.249-0.745; p < .05).

CONCLUSIONS

The present MR study provides exploratory evidence suggesting potential causal associations between GLP1R agonism and appendicular lean mass, whole-body fat-free mass, lung function (FVC), and myocardial infarction. Given the exploratory nature of these findings and the limitations of the MR methodology, further research is needed to validate these results and investigate the underlying biological mechanisms.