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Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2011 Nov; Vol. 58 (5), pp. 776-83. Date of Electronic Publication: 2011 Sep 19. - Publication Year :
- 2011
-
Abstract
- To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m(2) (IQR: 0.16-0.50 mL/min per 1.73 m(2)) on combined therapy, 0.36 mL/min per 1.73 m(2) (IQR: 0.18-0.53 mL/min per 1.73 m(2)) on delapril, and 0.30 mL/min per 1.73 m(2) (IQR: 0.12-0.50 mL/min per 1.73 m(2)) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04-0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07-0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24-0.87; P=0.017) and 0.52 (0.27-0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.
- Subjects :
- Adult
Aged
Angiotensin-Converting Enzyme Inhibitors administration & dosage
Angiotensin-Converting Enzyme Inhibitors adverse effects
Blood Glucose analysis
Body Mass Index
Calcium Channel Blockers administration & dosage
Calcium Channel Blockers adverse effects
Diabetes Mellitus, Type 2 diagnosis
Diabetes Mellitus, Type 2 drug therapy
Diabetic Nephropathies prevention & control
Dihydropyridines adverse effects
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Humans
Hypertension diagnosis
Hypertension mortality
Indans adverse effects
Kidney Function Tests
Male
Middle Aged
Nitrobenzenes
Piperazines
Prognosis
Risk Assessment
Severity of Illness Index
Survival Rate
Treatment Outcome
Blood Glucose drug effects
Diabetes Mellitus, Type 2 complications
Dihydropyridines administration & dosage
Hypertension complications
Hypertension drug therapy
Indans administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 58
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 21931073
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.111.174474