Pharmacogenetics and future strategies in treating hyperglycaemia in diabetes.

This review focuses on current evidence for pharmacogenetics for the 3 commonly used drug classes in treating diabetes: metformin, sulphonylureas and thiazolidinediones. Currently, metformin pharmacogenetics is focussing on drug transport with the recent finding that variation in OCT transporters might affect metformin response. An aetiological approach has identified monogenic patients with diabetes due to TCF1 mutations who are particularly sensitive to the hypoglycaemic effects of sulphonylureas, and KCNJ11 or ABCC8 mutations in which sulphonylureas can be used in place of insulin treatment. In Type 2 diabetes sulphonylurea response has been shown to be associated with variants TCF7L2 associated with type 2 diabetes risk. For thiazolidinediones, focus has been on PPARgamma variants although with no consistent result. Genome wide association studies offer great potential to unravel what genetic factors influence response and side effects of diabetes therapies. Large numbers of well phenotyped patients for response and side effect as well as similarly sized similarly phenotyped replication cohorts are required. Establishing such cohorts is a priority in diabetes pharmacogenetics research.