Table 4: Clinical studies of AGE-RAGE inhibitory effects of anti-hypertensive drugs.
| Therapeutic drug | Experimental design | Patient characteristics and treatment groups | Treatment duration | Major findings | Reference |
| Eprosartan (ARB) | Randomised, parallel group study | Hypertension, diastolic dysfunction (n = 97) • 600 mg eprosartan (n = 47) • Other hypertensive drugs (n = 50) |
6 months | • No beneficial treatment effect was detected in CML, CEL and pentosidine levels. | [104] |
| Irbesartan (ARB) | Double-blind RCT | T2DM, microalbuminuria (n = 264) • Placebo (n = 125) • 300 mg irbesartan (n = 139) |
2 years | • No beneficial treatment effect was detected in CML and CEL. | [103] |
| Valsartan (ARB) | Single-arm | T2DM, hypertension (n = 15) • 40 mg valsartan |
6 months | • AGE level and urine microalbumin level were decreased but oxidative markers remained unchanged. | [101] |
| Valsartan (ARB) | Single-arm | T2DM, microalbuminuria, hypertension (n = 12) • 80-160 mg valsartan |
6 months | • Plasma and urinary pentosidine, CML and 15-F2t-isoprostanes were reduced. • Plasma and urinary malondialdehyde was unchanged. |
[99] |
| Olmesartan (ARB) Telmisartan (ARB) |
Randomised, parallel group study | Hypertensive, on dialysis (n = 24) • 20 mg olmesartan (n = 12) • 40 mg telmisartan (n = 12) |
24 weeks | • Olmesartan decreased systolic blood pressure, pentosidine and CML compared to telmisartan. | [100] |
| Ramipril (ACE inhibitor) | Nonrandomised, parallel group study | Non-diabetic nephropathy (n = 19) • 2.5-5 mg ramipril (n = 12) • Other anti-hypertensive drugs (n = 7) |
2 months | • AGE fluorescence, AOPP decreased and malondialdehyde by ramipril therapy but CML remained unchanged. | [118] |
| Irbesartan (ARB) Amlodipine (CCB) |
Double-blind RCT | T2DM, nephropathy (n = 196) • Placebo (n = 70) • 300 mg irbesartan (n = 65) • 10 mg amlodipine (n = 61) |
2 years | • No beneficial treatment effect was detected in pentosidine and CML levels for ARB and CCB. | [102] |
| Azelnidipine (CCB) Amlodipine (CCB) |
Randomised, parallel group study | Non-diabetic chronic kidney disease (n = 30) • 16 mg azelnidipine (n = 15) • 5 mg amlodipine (n = 15) |
6 months | • Azeldipine decreased AGE, sRAGE, proteinuria and urinary levels of liver-type fatty acid binding protein but not amlodipine. | [120] |
| Nifedipine- Telmisartan combined therapy | Single-arm | Hypertensive, microalbuminuria (n = 262) • 20 mg nifedipine-80 mg telmisartan combined therapy |
24 weeks | • Significant increase in plasma sRAGE was observed. | [121] |
ACE: Angiotensin Converting Enzyme; AGE: Advanced Glycation End Product; AOPP: Advanced Oxidation Protein Product; ARB: Angiotension II Receptor Blocker; CCB: Calcium Channel Block; CEL: Carboxyethyllysine; CML: Carboxymethyllysine; RCT: Randomised Controlled Trial; sRAGE: Soluble Receptor for Advanced Glycation End Product; T1DM: Type 1 Diabetes Mellitus; T2DM: Type 2 Diabetes Mellitus.