Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double‐blind placebo‐controlled multicenter clinical study

Abstract

Background: Persistent proteinuria is an important factor contributing to the progression of diabetic nephropathy. The present randomized double-blind placebo-controlled multicenter clinical study evaluated the efficacy and safety of telmisartan combined with the antioxidant probucol in reducing urinary protein levels in patients with type 2 diabetes (T2D). Methods: Patients with T2D and 24-h proteinuria 0.5-3 g were enrolled in the study and randomly assigned to one of two groups: a telmisartan or a probucol + telmisartan group. Both groups were given telmisartan 80 mg q.d. for 48 weeks. The probucol + telmisartan group was given probucol 500 mg b.i.d. for the first 24 weeks, with the dosage then reduced to 250 mg b.i.d. for the remaining 24 weeks. The telmisartan group was given probucol placebo. Results: In all, 160 patients were enrolled in the present study. The 24-h proteinuria levels were significantly reduced in the probucol + telmisartan compared with telmisartan group. For patients with baseline 24-h proteinuria levels <1.0 g, both treatments resulted in significant reductions in 24-h proteinuria levels after 48 weeks treatment. However, in patients with baseline 24-h proteinuria levels ≥1.0 g, 24-h proteinuria levels after 48 weeks treatment were only reduced in the probucol + telmisartan group. There was no significant difference between the two groups for either adverse cardiovascular or other events. Conclusions: In patients with diabetic nephropathy, probucol combined with telmisartan more effectively reduces urinary protein levels than telmisartan alone.

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin–Angiotensin System Blockade

“…Therefore, the study was not designed to examine the additional benefit of probucol when added to the optimized dosage of ACEIs/ARBs, and the proportion of subjects who used ACEIs/ARBs before the run-in period was not provided. 12 In the current study, probucol did not decrease the oxidized LDL level (Figure 3). However, this finding does not preclude an antioxidative effect of probucol because it has been suggested that the protective effect of probucol depends not on its ability to inhibit lipid oxidation, but on its ability to induce the stress-induced anti-inflammatory enzyme heme oxygenase-1.…”

“…In a recent study that showed the superior efficacy of probucol plus telmisartan to that of telmisartan alone in terms of proteinuria extent, the dosage of probucol was 1000 mg/d (500 mg twice daily) for the first 24 weeks and then 500 mg/d (250 mg twice daily) for an additional 24 weeks. 12 The protective effect of probucol in contrast-induced acute kidney injury has also been reported [15][16][17] presumably because of the antioxidant effect of probucol. The dosage of probucol in these studies, 1000 mg orally before the procedure and then 500 mg twice daily for 3 days, was much higher than that of the current study.…”

“…10,11 A recent study by Zhu et al 12 additionally reported the superior efficacy of probucol plus telmisartan to that of telmisartan alone in terms of proteinuria extent. In the study by Zhu et al, 12 a fixed dosage of telmisartan (80 mg once daily) was given with or without probucol after a 4-week run-in period during which a fixed dosage of telmisartan (80 mg once daily) was given and other ACEIs/ARBs were stopped if they were used before the study period.…”

“…In the study by Zhu et al, 12 a fixed dosage of telmisartan (80 mg once daily) was given with or without probucol after a 4-week run-in period during which a fixed dosage of telmisartan (80 mg once daily) was given and other ACEIs/ARBs were stopped if they were used before the study period. Therefore, the study was not designed to examine the additional benefit of probucol when added to the optimized dosage of ACEIs/ARBs, and the proportion of subjects who used ACEIs/ARBs before the run-in period was not provided.…”

Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications

“…[ 3 ] On the other hand, the combinations of ARBs with natural products such as curcumin and resveratrol have been found to be more effective in reducing metabolic perturbation, inflammation, insulin resistance (IR), hypertension, and many other complications associated with diabetes. [ 4 5 ] Recently, we have reported that combination of telmisartan with a functional food ingredient, esculetin-prevented oxidative stress, cardiac fibrosis, and vascular stiffness in high-fat diet (HFD) induced IR condition. [ 6 ]…”