The Effect of Trandolapril and Its Fixed-Dose Combination With Verapamil on Proteinuria in Normotensive Adults With Type 2 Diabetes

Abstract

OBJECTIVE -To compare the effect of fixed-dose trandolapril-verapamil (FDTV) with that of trandolapril on proteinuria in normotensive, type 2 diabetic patients. RESEARCH DESIGN AND METHODS-A total of 60 normotensive, type 2 diabetic patients with 24-h proteinuria Ͼ300 mg were randomly assigned to two groups for open-label treatment. One group received 2 mg trandolapril/180 mg verapamil FDTV once daily; the other group received 2 mg trandolapril once daily. Study drugs were administered for 6 months in both groups. Creatinine clearance and 24-h urinary protein excretion were measured at the beginning and the end of the study. Patients were evaluated monthly for blood pressure, fasting blood glucose level, heart rate, and adverse events. Statistical analysis was performed using ANOVA.RESULTS -Both groups experienced a statistically significant (P Ͻ 0.005) mean decrease in mean proteinuria from baseline: FDTV ([mean Ϯ SD] 1,200 Ϯ 200 to 540 Ϯ 79 mg; P Ͻ 0.001) and trandolapril (1,105 Ϯ 212 to 750.9 Ϯ 134 mg; P Ͻ 0.005). A significantly greater reduction from baseline in proteinuria was observed in the FDTV group compared with the trandolapril group. Patients who received trandolapril experienced a statistically significant (P Ͻ 0.05) decrease in mean creatinine clearance (91.1 Ϯ 3.4 to 75.3 Ϯ 3 ml/min; P Ͻ 0.05) compared with patients who received FDTV (88.3 Ϯ 3.6 to 82.9 Ϯ 3.5 ml/min; P Ͼ 0.05). Final fasting blood glucose was significantly lower in the FDTV group (139 Ϯ 19) compared with the trandolapril group (154 Ϯ 22; P Ͻ 0.001). No significant differences were observed between the two groups in mean baseline or final measurements of blood pressure, mean heart rate, or frequency of adverse events.CONCLUSIONS -Our results suggest that FDTV is more effective than trandolapril in reducing proteinuria in normotensive, type 2 diabetic patients. This effect on proteinuria is not related with blood pressure reduction. Diabetes Care 27:1688 -1691, 2004T he prevalence of diabetic nephropathy is ϳ30% in patients with type 2 diabetes after 20 -30 years. It is the most common cause of end-stage renal disease and increases the mortality rate in those patients (1,2). In diabetic patients, proteinuria levels are related not only to the progression of nephropathy but also to cardiovascular mortality, and in Mexico, proteinuria has a prevalence of 9.3% in type 2 diabetic normotensive patients (3). In turn, reduction of proteinuria or delay in its progression may delay the onset of end-stage renal disease.Recent clinical studies have shown that several therapeutic strategies are available to delay the progression of diabetic nephropathy: rigorous glycemic control, aggressive antihypertensive control to achieve blood pressure values Ͻ130/80 mmHg, and blockade of the renin-angiotensin system (1).To decrease morbidity and mortality due to diabetic nephropathy, early detection of patients at risk is critical, as is the application of all necessary therapeutic measures. The 2003 European Society of Hypertension-European Society of C...

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“…However, we found that normotensive diabetes patients treated with the fixed-dose TV combination (for nephroprotection) reached a better fasting glycemic control than normotensive diabetes patients treated with monotherapy with trandolapril after 6 months of treatment. In that trial no patient received diuretics,31 leading us to hypothesize that the fixed-dose TV combination may have a role in glycemic control unrelated to its antihypertensive effect.…”

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“…Of interest, the trandolapril/verapamil treatment decreased the incidence of microalbuminuria to a similar extent to trandolapril alone in type 2 hypertensive normoalbuminuric diabetic subjects 23 . Finally, in normotensive macroalbuminuric type 2 diabetic subjects, this combination did not alter the glomerular filtration rate, which was conversely significantly reduced in the trandolapril group 21 …”

“…Specifically, the verapamil/trandolapril combination significantly reduced albuminuria to a greater extent when compared with atenolol/chlorthalidone 18 and to a similar degree in the enalapril/hydrochlorothiazide 20 treatment group. Furthermore, this specific combination, when compared with trandolapril 21,22 or verapamil 22 as monotherapies, had an additional effect in reducing proteinuria despite similar BP levels in both normotensive 21 and hypertensive 22 macroalbuminuric type 2 diabetic patients. Of interest, the trandolapril/verapamil treatment decreased the incidence of microalbuminuria to a similar extent to trandolapril alone in type 2 hypertensive normoalbuminuric diabetic subjects 23 .…”