Renal Protective Effects of Combination of Diltiazem and ACEI/ARB on the Progression of Diabetic Nephropathy: Randomized Controlled Trial.

BACKGROUND

Strict control of blood sugar and maintenance of normal blood pressure levels are the standard treatments shown to delay the progression of diabetic nephropathy in type 2 diabetic patients. The recommended antihypertensive medications for diabetic nephropathy are angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Previous studies have shown that a non-dihydropyridine calcium channel blocker (diltiazem) could reduce urinary protein excretion in type 2 diabetic patients.

OBJECTIVE

To evaluate the effects of the combinations of diltiazem and ACEI/ARB treatment compared with ACEI/ARB alone in type 2 diabetic patients with diabetic nephropathy.

MATERIAL AND METHOD: A prospective, randomized, double-blind, placebo-controlled multicenter trial was conducted at the out-patient departments of Rajavithi Hospital (Bangkok) and Ban-phaeo Hospital (Samut Sakhon). A total of 106 type 2 diabetic patients with hypertension and urine protein/creatinine (UPCr) >0.3 gm/gm who had received ACE/ARB were randomized into two groups: a diltiazem group (ACEI/ARB + sustained-release diltiazem 120 mg daily) (50 cases) and a placebo group (ACEI/ARB + placebo) (56 cases). Intention-to-treat analysis was utilized with the data of patients who withdrew from the study before its completion date.

RESULTS

39 cases in the diltiazem group (78.0%) and 38 in the placebo group (67.9%) completed the 1-year treatment. The diltiazem group achieved better preservation of glomerular filtration rate and had lower proteinuria than the placebo group (p<0.05), whereas blood pressure was similar in the two groups. Four patients in the diltiazem group and one patient in the placebo group developed severe pedal edema and discontinue treatment.

CONCLUSION

A combination of diltiazem and ACE/ARB could reduce proteinuria and preserve kidney function in type 2 diabetic patients with diabetic nephropathy.