Pharmacogenetics in type 2 diabetes: potential implications for clinical practice

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

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		??

For details, see authoritative reviews [71–74] and recent clinical guidelines [75–77]. DPP-IV, dipeptidyl peptidase-IV; GI, gastrointestinal tract; GLP-1, glucagon-like peptide-1; IGF, insulin-like growth factor.

ISSN: 1756-994X