Pharmacogenetics of the Glucagon-like Peptide-1 Receptor Agonist Liraglutide: A Step Towards Personalized Type 2 Diabetes Management

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence and a significant burden of long-term complications. Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) are a novel treatment option for T2DM, exerting optimal effects on glucose control and weight loss, and pleiotropic actions. Pharmacogenetics, a promising research field of precision medicine, investigates how gene variations can affect individual response to drug therapy, assuming that the diverse genetic architecture of patients with T2DM could be partly associated with the considerable inter-individual variability in the therapeutic response to GLP-1 RAs. This review aims to summarize current evidence related to T2DM risk variants, affecting the incretin pathway, focus on the pharmacogenetics of the GLP-1 RA liraglutide, and discuss their potential clinical implications in the management of this complex disorder. Methods: A literature search was performed using electronic biomedical databases, and the findings of key studies are summarized and discussed in this narrative review. Results: Available evidence suggests the involvement of genetic polymorphisms in GLP-1 Rgene in variation in glycemic response, metabolic parameters and gastric emptying in people treated with liraglutide. Polymorphisms in CNR1, CTRB1/2, TMEM114 and CHST3 loci were also shown to be implicated in the disturbance of the incretin homeostasis in T2DM. These findings warrant further investigation by future studies. Conclusion: Robust findings from pharmacogenetic studies might be used to identify good responders to liraglutide treatment, in terms of both glycemic and weight control, thus reinforcing the patient-centered approach of T2DM management.