Genetic Variants Associated with Response to GLP-1 Receptor Agonists in Diabetes and Obesity

Genetic variation may contribute to interindividual differences in the efficacy and tolerability of glucagon-like peptide-1 receptor agonists (GLP-1RAs), although the available evidence remains limited. Certain gene variants may underlie variability in glycemic control and weight loss outcomes among patients treated with GLP-1RAs for diabetes and/or obesity. A better understanding of these genetic variations could have significant implications for the development of personalized medicine, contributing to predicting patient responses to GLP-1RAs. Within this review, we collected and synthesized information from different studies about genetic variants that have been reported to be associated with altered therapeutic response to GLP-1RAs, mostly in GLP1R, but also in TCF7L2 and PNPLA3 genes. For the same variants, the differences obtained in the outcomes were, however, inconsistent between studies. Such disparities may partly reflect the diversity of the outcomes analyzed, the specific GLP-1RA in use, and/or the characteristics of each population. Additional genes, such as PPARD, WFS1 and VTRNA2-1, exhibited differences in at least one study. Although still limited, considering the fast expansion of the prescription of this therapeutic class, these results reflect the need for additional studies, before enabling the implementation of pharmacogenetics in clinical practice.