Renal Protective Effects of Combination of Diltiazem and ACEI/ARB on the Progression of Diabetic Nephropathy: Randomized Controlled Trial
Udom Krairittichai MD*, Veerasak Sarinnapakorn MD*, Rungrawee Mahannopkul MD**, Ploypassorn Ainwan BBA*
Affiliation : * Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand ** Department of Medicine, Ban-phaeo Hospital, Samutsakorn, Thailand
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.
Keywords : Diabetic nephropathy, Diltiazem
