Table 1.
Recent clinical evidence of therapeutic interventions in advanced glycation products and their complications.
| Mechanism of Action | Drug | Methodology | Results | Author [REF] |
|---|---|---|---|---|
| Inhibition of the endogenous formation of AGEs | Benfotiamine and Pyridoxamine | Randomized, double-blinded controlled by placebo trial, which included 30 patients with primary osteoarthritis divided randomly between two groups to receive tablets of inhibitors of AGEs (benfotiamine (50 mg) + PM (50 mg) + methylcobalamin (500 mg)) or placebo tablets, three times a day. | Significant decrease in serum levels and fluorescence of AGEs. Decreased pain and inflammation. Increase in daily activity and mobility in patients with osteoarthritis. | Garg S et al. (2013) [130] |
| Pioglitazone and Metformin | Randomized, open parallel-groups trial, performed in patients recently diagnosticated with DM2, who were given 30 mg/day of pioglitazone (n = 30), 1000 mg/day of metformin (n = 50) or not any drugs (n = 49). | In both treated groups with either pioglitazone or metformin was observed a statistically significant decrease in levels of AOPP and AGEs, besides causing an increase in FRAP (a marker of plasma antioxidant capacity). | Mirmiranpour H et al. (2013) [131] | |
| Enalapril and Lercanidipine | Randomized, double-blinded trial, which included 359 ambulatory patients <65 years of age, first-diagnosed with essential hypertension and without treatment, divided between three groups, who were randomly given: enalapril 20 mg/day (n = 126), lercanidipine 10 mg/day (n = 115), or enalapril + lercanidipine 20/10 mg/day (118), in order to assess their effects in markers of cardiovascular risk. | All treatments showed a significant increase in levels of sRAGE, which was higher in patients treated with enalapril + lercanidipine.Significant reduction of levels of TNF-α and US-CRP in patients treated with enalapril + lercanidipine | Derosa G et al. (2014) [132] | |
| Benfotiamine | Randomized, double-blinded, controlled trial, which included 41 patients with DM2 without complications, who were randomly given 900 mg/day of benfotiamine or 900 mg/day of a placebo, to assess their effect on levels of AGEs and sRAGE. | Patients treated with benfotiamine had a statistically significant decrease in levels of carboxymethyl-lysine. There were no statistically significant differences in levels of sRAGE. | Contreras C et al. (2017) [133] | |
| Breakage and Reversal of preformed AGEs | Alagebrium (ALT-711) | Randomized, double-blinded, controlled by placebo prospective study, performed in 57 healthy subjects over 60 years of age, which were randomly divided between 4 groups: sedentary + placebo, sedentary + alagebrium (200 mg/day), exercise + placebo, and exercise + alagebrium in order to assess their effect in hemodynamics, function, and structure of the left ventricle. | Alagebrium led to a moderate improvement in rigidity of the left ventricle, which was more prominent when it was combined with physical activity. | Fujimoto N et al. (2013) [134] |
| Alagebrium | Randomized, controlled by placebo trial, which included 47 older subjects previously sedentary, who were divided between 4 types of interventions: Exercise + Alagebrium (200 mg/day), Exercise + Placebo, Alagebrium (200 mg/day), and Exercise aiming to examine their effect over endothelial function, arterial stiffness, and cardiovascular risk. | There were no improvements in endothelial function or arterial stiffness in any of the four groups. | Oudegeest-Sander M et al. (2013) [135] | |
| Inhibition of the absorption of exogenous AGEs | Sevelamer carbonate | Randomized, open, single-blinded trial, which included 117 patients with T2DM and diabetic nephropathy in stages 2 to 4, who were given sevelamer carbonate (1600 mg) or calcium carbonate (1200 mg), three times a day, to measure their effects in the AGE–RAGE axis and onto oxidative stress. | Patients treated with sevelamer carbonate showed a significant reduction of both circulating and intracellular AGEs (carboxymethyl-lysine and methylglyoxal).It was also observed a significant increase in antioxidant defenses and reduction of pro-oxidant molecules. | Yubero-Serrano et al. (2015) [136] |
AGEs, advanced glycation end products; AOPP, advanced oxidation protein products; T2DM, Type 2 diabetes mellitus; FRAP, Ferritin reducing ability of plasma; HbA1C, glycated hemoglobin; RAGE, receptor for advanced glycation end products; sRAGE, soluble RAGE; TNF-α, tumor necrosis factor-α; US-CRP, ultra-sensitive C-Reactive Protein; and sVCAM, soluble vascular cell adhesion molecule-1.