Pharmacogenetics of Oral Antidiabetic Therapy

Abstract

Type 2 diabetes prevalence is still on the rise worldwide. Antidiabetic drugs are widely prescribed to patients with Type 2 diabetes. Most patients start with metformin which is mostly well tolerated. However, a high percentage of patients fail to achieve glycemic control. The effectiveness of metformin as well as most other antidiabetic drugs depends among other factors on interindividual genetic differences that are up to now ignored in the treatment of Type 2 diabetes. Interestingly, many genes influencing the effectiveness of antidiabetic drugs are Type 2 diabetes risk genes making matters worse. Here, we shed light on these interindividual genetic differences.

The influence of SLC22A1 rs622342 and ABCC8 rs757110 genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian patients with type 2 diabetes

“…Several guidelines, including ADA, recommended achieving a range of 6.5–7% for good glycemic control and minimal risks for the associated complications 38 . Pharmacogenetic studies could help in investigating and identifying those variabilities seen in practice between patients receiving oral hypoglycemic agents 11 , 12 .…”

“…Both drugs decrease blood glucose by different mechanisms, metformin decreases the hepatic glucose production, and acts as insulin sensitizer, while sulfonylureas lower blood glucose by increasing insulin secretion 10 . There is a great variation in response to many oral hypoglycemics, interestingly up to 40% of inter-individual variabilities could be explained by genetic factors 11 , 12 .…”

Pharmacogenetics of Metformin

“…Metformin might induce lactic acidosis in patients with renal insufficiency, therefore it is not prescribed in this subgroup of patients with T2D. 5 To Other mechanisms of the hypoglycemic effect of metformin include glucoagon-dependent antagonism of glucose output from hepatocytes by reducing cyclic AMP production, and inhibition of glucose hepatic mitochondrial glycerophosphate dehydrogenase.…”

rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

“…An updated review concluded that the addition of a sulfonylurea to metformin persists the most cost-effective second-line therapy for patients when compared to other drugs (Sodium-glucose co-transporter-2 inhibitors, dipeptidyl-peptidase inhibitors and Glucagon-like peptide-1receptor agonist) [ 11 ]. Despite this, it is becoming increasingly evident that the treatment outcome with oral anti-diabetics differs strongly between individuals and that a personalized approach would make sense [ 12 ].…”