Table 1—

Therapeutic agents targeting AGEs: human and animal data

Category of therapy: human studiesMost advanced stage of trials as relates to AGEsTrial resultsSafety concerns
Prevent AGE formation
Therapeutic entity
AminoguanidineHuman, phase III↓nephropathy, ↓retinopathy↑glomerulonephritis, ↓vitamin B6, ↓iNOS
BenfotiamineHuman, phase II↓neuropathyNone reported
AR inhibitors (epalrestat, zopolrestat)Human, phase II↓AGE levels, ↓neuropathy, ↑esophageal motilityNone reported
AGE cross-link disrupter
Therapeutic entity
ALT-711 (alagebrium chloride)Human, phase III↓arterial stiffness, ↓pulse pressure, breaks cross-links formed by AGEs, ↑diastolic heart functionNone reported
Antihypertensive
Therapeutic entity
ARBHuman, phase III↓macrophages in carotid artery plaque↓GFR, rare angioedema
ACE inhibitorHuman, phase II↓RAGE levels↓GFR, rare angioedema
Dietary factors
Therapeutic entity
Low-AGE dietHuman data, stage N/A↓AGE levels, ↓C-reactive proteinNone reported
Prevent AGE formation
Therapeutic entity
ALT-946Animal (diabetic rats)↓nephropathy better than aminoguanidineNone reported
LR-90Animal (diabetic rats)↓nephropathy, ↓oxidative stress↑weight gain
OPB 9195Animal (diabetic rats)↓stenosis after vessel injury, ↓nephropathy↓ vitamin B6
PARP inhibitorsAnimal (diabetic rats)↓endothelial dysfunction, ↓diastolic dysfunction, ↓neuropathyNone reported
PyridoxamineAnimal (diabetic rats)↓nephropathy, ↓cholesterol, ↓weightNone reported
AGE cross-link disrupter
Therapeutic entity
PTBAnimal (diabetic rats)↓AGEsNone reported
AGE binder
Therapeutic entity
Soluble RAGEAnimal (diabetic mice)↓stenosis after vessel injury, ↓neuropathyNone reported
LysozymeAnimal (diabetic and apolipoprotein E–null mice)↓AGEs, ↓nephropathy, ↓atherosclerosisNone reported
Antioxidants
Therapeutic entity
Green teaAnimal (diabetic rats)↑AGEs, ↑AGE cross-linksNone reported
Vitamins E and CAnimal (diabetic rats)↑AGEs, ↑AGE cross-links↑CV morbidity from vitamin E >400 IU
Oral hypoglycemic agents
Therapeutic entity
MetforminAnimal (diabetic rats)↓AGEs, ↓AGE cross-linksLactic acidosis
PioglitazoneIn vitro↓AGEs, ↓AGE cross-links↑hepatitis, ↑CHF if susceptible
  • AR, aldose reductase; CHF, congestive heart failure; CV, cardiovascular; GFR, glomerular filtration rate; iNOS, inducible nitric oxide synthase; PTB, N-phenacylthiazolium bromide; TZD, thiazolidinedione.