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.
| Original language | English |
|---|---|
| Pages (from-to) | 776-783 |
| Number of pages | 8 |
| Journal | Hypertension |
| Volume | 58 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Nov 2011 |
Fingerprint
Keywords
- ACE inhibitors
- Calcium channel blockers
- Cardiovascular complications
- Diabetic nephropathy
- Diabetic neuropathy
- Diabetic retinopathy
- Manidipine
ASJC Scopus subject areas
- Internal Medicine
Cite this
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. / Ruggenenti, Piero; Lauria, Giuseppe; Iliev, Ilian Petrov; Fassi, Anna; Ilieva, Aneliya Parvanova; Rota, Stefano; Chiurchiu, Carlos; Barlovic, Drazenka Pongrac; Sghirlanzoni, Angelo; Lombardi, Raffaella; Penza, Paola; Cavaletti, Guido; Piatti, Maria Luisa; Frigeni, Barbara; Filipponi, Marco; Rubis, Nadia; Noris, Greta; Motterlini, Nicola; Ene-Iordache, Bogdan; Gaspari, Flavio; Perna, Annalisa; Zaletel, Jelka; Bossi, Antonio; Dodesini, Alessandro Roberto; Trevisan, Roberto; Remuzzi, Giuseppe.
In: Hypertension, Vol. 58, No. 5, 11.2011, p. 776-783.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus
T2 - The delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial
AU - Ruggenenti, Piero
AU - Lauria, Giuseppe
AU - Iliev, Ilian Petrov
AU - Fassi, Anna
AU - Ilieva, Aneliya Parvanova
AU - Rota, Stefano
AU - Chiurchiu, Carlos
AU - Barlovic, Drazenka Pongrac
AU - Sghirlanzoni, Angelo
AU - Lombardi, Raffaella
AU - Penza, Paola
AU - Cavaletti, Guido
AU - Piatti, Maria Luisa
AU - Frigeni, Barbara
AU - Filipponi, Marco
AU - Rubis, Nadia
AU - Noris, Greta
AU - Motterlini, Nicola
AU - Ene-Iordache, Bogdan
AU - Gaspari, Flavio
AU - Perna, Annalisa
AU - Zaletel, Jelka
AU - Bossi, Antonio
AU - Dodesini, Alessandro Roberto
AU - Trevisan, Roberto
AU - Remuzzi, Giuseppe
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - ACE inhibitors
KW - Calcium channel blockers
KW - Cardiovascular complications
KW - Diabetic nephropathy
KW - Diabetic neuropathy
KW - Diabetic retinopathy
KW - Manidipine
UR - http://www.scopus.com/inward/record.url?scp=83155180436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83155180436&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.111.174474
DO - 10.1161/HYPERTENSIONAHA.111.174474
M3 - Article
C2 - 21931073
AN - SCOPUS:83155180436
VL - 58
SP - 776
EP - 783
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 5
ER -