Skip to main content

Table 2 Targets, clinical responses and candidate genes involved in drug response of anti-diabetes medications

From: Pharmacogenetics in type 2 diabetes: potential implications for clinical practice

Drugs Mechanism of action Main effect(s) Potential adverse events Candidate genes putatively affecting response
Sulfonylureas ATP-dependent K channel inhibition ↑ Insulin secretion
↓ Glucagon secretion
Hypoglycemia,
allergic reaction to sulfa drugs
CYP2C9, ABCC8, KCNJ11, TCF7L2
Metformin AMP-dependent kinase (AMPK) activation ↑ Insulin sensitivity
↓ Hepatic gluconeogenesis
Lactic acidosis SLC22A1, SLC47A1, ATM
Thiazolidinediones Enhance PPARγ binding to its DNA response element ↑ Glucose uptake by skeletal muscle
↑ Lipolysis
↓ Hepatic glucose output
Fluid overload, congestive heart failure, fractures, hepatotoxicity,
bladder cancer
ADIPOQ, CYP2C8
Insulin Insulin/IGF-1 receptor pathway ↑ Tissue glucose uptake Hypoglycemia ??
Meglitinides ATP-dependent K channel inhibition ↑ Insulin secretion
↓ Glucagon secretion
Hypoglycemia ??
α-Glucosidase inhibitors Inhibit pancreatic α-amylase and intestinal α-glucosidase Glucose absorption by GI tract Hypoglycemia ??
Amylin minetics Amylin receptor pathway ↓ Gastric emptying rate
↑ Insulin secretion
↓ Glucagon secretion
Hypoglycemia ??
GLP-1 mimetics GLP-1 receptor pathway ↑ Glucose-dependent insulin secretion
↓ Gastric emptying rate
↑ Satiety
↓ Glucagon secretion
Nausea, vomiting, hypoglycemia, acute pancreatitis,
angioedema, anaphylaxis
??
DPP-IV inhibitors GLP-1 receptor pathway ↑ Glucose-dependent insulin secretion   ??
  1. For details, see authoritative reviews [7174] and recent clinical guidelines [7577]. DPP-IV, dipeptidyl peptidase-IV; GI, gastrointestinal tract; GLP-1, glucagon-like peptide-1; IGF, insulin-like growth factor.