Treatment of hypertensive patients with diabetes: beyond blood pressure control and focus on manidipine.

Renin-angiotensin system inhibitors should be considered as the first-line therapy in the treatment of patients with hypertension and diabetes. However, most of the diabetic subjects with hypertension require at least two drugs to achieve blood pressure targets. The ACCOMPLISH trial suggested that the best combination in the treatment of high-risk hypertensive patients should include a renin-angiotensin system inhibitor and a dihydropyridine. However, not all dihydropyridines block the same receptors. Those dihydropyridines that block T-type calcium channel blockers may provide additional advantages. A number of studies suggest that compared with amlodipine, manidipine have the same antihypertensive efficacy, but with a lesser risk of ankle edema. In addition, manidipine, but not amlodipine, significantly reduces urinary albumin excretion rates.

Effects of manidipine and its combination with an ACE inhibitor on insulin sensitivity and metabolic, inflammatory and prothrombotic markers in hypertensive patients with metabolic syndrome: the MARCADOR study.

BACKGROUND AND OBJECTIVE: Metabolic syndrome is common in patients with hypertension and increases the risk of developing diabetes mellitus. The objective of this study (the MARCADOR study) was to compare the effects of manidipine 20 mg with the extemporary combination of manidipine 10 mg/lisinopril 10 mg, amlodipine 10 mg and telmisartan 80 mg on insulin sensitivity, as well as metabolic, inflammatory and prothrombotic markers, in hypertensive non-diabetic patients with metabolic syndrome. METHODS: This study had a prospective, randomized, open-label, blinded endpoint (PROBE) design. A total of 120 patients aged 35-75 years with stage I-II essential hypertension (systolic blood pressure [BP] 140-179 mmHg, diastolic BP 90-109 mmHg) and metabolic syndrome were recruited from general practitioner clinics in Northern Gran Canaria Island, Spain and randomized to receive amlodipine 10 mg (n = 30), telmisartan 80 mg (n = 30), manidipine 20 mg (n = 30) or (low-dose) manidipine 10 mg/lisinopril 10 mg (n = 30), all administered once daily. At baseline and after 14 weeks of treatment, BP, insulin sensitivity, lipid profile, and albumin and metanephrin excretion as well as several other metabolic, inflammatory, prothrombotic and growth/adhesion markers were measured. The primary endpoint was the change in insulin sensitivity. RESULTS: A total of 115 patients completed the study. All treatments significantly lowered BP from baseline. Compared with amlodipine, manidipine had significantly superior effects (p < 0.05) on insulin resistance (-26.5% vs -3.0%), albumin/creatinine ratio (-28.2% vs -3.6%), low-density lipoprotein (LDL) cholesterol (-6.8% vs +1.7%), and several other metabolic, inflammatory and prothrombotic markers. Manidipine was associated with a slightly greater increase in insulin sensitivity than manidipine/lisinopril, but manidipine/lisinopril was significantly more effective than manidipine and telmisartan for improving a number of metabolic, inflammatory, prothrombotic and growth/adhesion markers. Amlodipine was associated with a significantly greater incidence of adverse effects compared with telmisartan, manidipine and manidipine/lisinopril (26.7% vs 3.3%, 3.3% and 13.3%, respectively). CONCLUSION: In patients with hypertension and metabolic syndrome, manidipine, both alone and in combination with the ACE inhibitor lisinopril, is significantly superior to amlodipine for improving insulin sensitivity as well as several metabolic, inflammatory and prothrombotic markers. Furthermore, the combination of manidipine and lisinopril appears to have greater efficacy than manidipine alone and telmisartan with respect to the improvement of metabolic, inflammatory and prothrombotic markers.