Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine

Type 2 diabetes mellitus (T2DM) is a chronic disease that has reached the levels of a global epidemic. In order to achieve optimal glucose control, it is often necessary to rely on combination therapy of multiple drugs or insulin because uncontrolled glucose levels result in T2DM progression and enhanced risk of complications and mortality. Several antihyperglycemic agents have been developed over time, and T2DM pharmacotherapy should be prescribed based on suitability for the individual patient's characteristics. Pharmacogenetics is the branch of genetics that investigates how our genome influences individual responses to drugs, therapeutic outcomes, and incidence of adverse effects. In this review, we evaluated the pharmacogenetic evidences currently available in the literature, and we identified the top informative genetic variants associated with response to the most common anti-diabetic drugs: metformin, DPP-4 inhibitors/GLP1R agonists, thiazolidinediones, and sulfonylureas/meglitinides. Overall, we found 40 polymorphisms for each drug class in a total of 71 loci, and we examined the possibility of encouraging genetic screening of these variants/loci in order to critically implement decision-making about the therapeutic approach through precision medicine strategies. It is possible then to anticipate that when the clinical practice will take advantage of the genetic information of the diabetic patients, this will provide a useful resource for the prevention of T2DM progression, enabling the identification of the precise drug that is most likely to be effective and safe for each patient and the reduction of the economic impact on a global scale.