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Background. The effect of angiotensin converting enzyme inhibitors (ACEi) on regression of retinopathy in type 2 diabetics is still ill defined. Methods. We compared the incidence of retinopathy regression in 90 hypertensive type 2 diabetics randomized to at least 3-year blinded ACEi with trandolapril (2 mg/day) or non-ACEi therapy who had preproliferative or proliferative retinopathy at baseline. Results. Over a median (interquartile range) follow-up period of 35.8 (12.4-60.7) months, retinopathy regressed in 27 patients (30.0%). Regression occurred in 18 of 42 patients (42.9%) on ACEi and in 9 of 48 (18.8%) on non-ACEi therapy (adjusted for predefined baseline covariates HR (95% CI): 2.75 (1.18-6.42), P = .0193). Concomitant treatment with or without Non-Dihydropyridine Calcium Channel Blockers (ndCCBs) did not appreciably affect the incidence of retinopathy regression. Conclusions. Unlike ndCCB, ACEi therapy may have an additional effect to that of intensified BP and metabolic control in promoting regression of diabetic retinopathy.

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 bu