Table 2.

Interventions targeting the advanced glycation end product (AGE) pathway

Mechanism of action	Therapeutic agent	Biological effects
Dietary restriction of AGE		Animal studies31,50,75–77
		Prevents/Improves
		Insulin resistance
		Abdominal obesity/body weight
		Diabetes mellitus type 2
		Diabetic nephropathy
		Diabetic-impaired wound healing
		Extends life span
		Human studies
		Healthy subjects78–80
		↓ Basal oxidative stress
		↓ Inflammation
		↓ Serum AGEs
		Improves markers of insulin resistance
		Subjects with diabetes or renal failure13,15,34
		↓ Serum AGEs
		↓ Inflammation
		Improves vascular function and insulin resistance
Blockage of AGE formation	Aminoguanidine83–85	Animal studies
		↓ Retinopathy
		↓ Nephropathy
		↓ Neuropathy
	N-(2-Acetamido Methyl) hydrazinecarboximide amide hydrochloride (ALT-946)86,87	↓ Nephropathy
	3-benzyloxycarbonylmethyl-4-methyl-thiazol-3-ium bromide (C36)88	↓ Diabetic cardiovascular dysfunction
	Pyridoxamine90,91	↓ Nephropathy
		↓ Dyslipidemia
Cross-link breakers	N-phenacylthiazolium (PTB)92	Animal studies
		↓ AGE
	Alagebrium (ALT-711)93,94,96	Animal studies
		↓ Diabetic cardiomyopathy and atherosclerosis
		↓ Nephropathy
		Human studies
		↓ Diastolic heart function
RAGE blockade	sRAGE100–103	Animal studies
		↓ Diabetic atherosclerosis
		and retinopathy (sRAGE)
	Antihypertensive drugs99	Antioxidative properties – prevention of diabetic vascular complications?
	PEDF99	Antioxidative properties
	Statins99	Antioxidative properties
	Bisphosphonates99	Antioxidative properties
	PARP inhibitors104,105	Animal studies
		↓ Early peripheral diabetic neuropathy Improve endothelial and myocardial function
Other agents	Kremezin (AST-120)106	↓ AGE levels in chronic renal failure

Abbreviations: PARP, poly(ADP-ribose) polymerase; PEDF, pigment-epithelium-derived factor; RAGE, receptor for advanced glycation end products; sRAGE, soluble receptor for advanced glycation end products; ↓, decrease/reduce.