lacidipine and Diabetes-Mellitus--Type-2

This study was carried out to assess whether with a similar degree of blood pressure reduction, Lisinopril compares favorably or otherwise with lacidipine in respect of effects on urinary albumin excretion and renal function as assessed by creatinine clearance, plasma creatinine, urea and electrolytes. Thirty hypertensive diabetic nephropathy patients with moderate hypertension were studied. After a 2-week washout period, they were allocated into two groups matched at baseline for age, sex, weight, blood pressure, and urinary albumin excretion rate as well as creatinine clearance. There were 8 males and 7 females in each group. One group received lisinopril (with furosemide if needed to control BP) and the other group received lacidipine. Staged increases in doses of antihypertensives were used until BP was controlled or maximum dose of 40 mg/day lisinopril or 8 mg/day lacidipine was reached. Furosemide was added to lisinopril if BP was not controlled at 40 mg/day. These medications were given for 12 weeks at the end of which measurements done at baseline were repeated. Comparison of baseline and end of study values of these parameters within the groups and between the two groups were made. Lisinopril group and lacidipine group achieved similar and highly significant reduction in blood pressure levels P < 0.001. There was reduction in urinary albumin excretion rate in both groups but this only reached statistical significance in the lisinopril group [480] [269] mg/day vs. 315 [202] mg/day P < 0.05] while for the lacidipine group it was not significant [491] [257] mg/day vs. 335 [182] mg/day P > 0.05]. However, comparison of albumin excretion rate between both groups at baseline and at end of the study did not show any significant difference, P > 0.1. With both drugs there is a tendency for creatinine clearance to increase and plasma creatinine to drop while plasma potassium tended to rise more with lisinopril than lacidipine but differences within and between both groups, did not reach statistical significance P > 0.05. In conclusion, blood pressure reduction was comparable in both drugs; both drugs reduced albuminuria but lisinopril appeared superior. Treatment with both drugs tended to increase creatinine clearance but both had no significant effects on blood sugar.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dihydropyridines; Disease Progression; Female; Humans; Hypertension; Lisinopril; Male; Metabolic Clearance Rate; Middle Aged; Potassium; Prospective Studies; Treatment Outcome; Urea

Antihypertensive treatment is frequently needed in type 2 diabetes. In this study we measured the rates of total, oxidative, and nonoxidative glucose disposal, glycogen synthesis, glycolysis, endogenous glucose production, and lipid oxidation using a 4-h euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 300 pmol/L) clamp in combination with a dual glucose tracer infusion ([3-(3)H]- and [U-14C] D-glucose) and indirect calorimetry in 40 nonobese subjects with type 2 diabetes. Subjects were studied twice: after a 4-week run-in period and after a 16-week period of double blind, randomized treatment with 4-6 mg/day lacidipine, a calcium channel blocker (n = 19), or 10-20 mg/day lisinopril, an angiotensin-converting enzyme inhibitor (n = 21). Antihypertensive treatment resulted in a significant increase in total glucose disposal during insulin clamp as well as in basal and insulin-stimulated nonoxidative glucose disposal rates. On the contrary, oxidative glucose disposal was significantly decreased by antihypertensive treatment, mainly in the basal state. The changes in glucose disposal rates were not significantly different in subjects treated with lacidipine and in those treated with lisinopril. The suppression of endogenous glucose production during insulin clamp was significantly greater after lacidipine than after lisinopril. These results suggest that treatment of subjects with type 2 diabetes with either lacidipine or lisinopril has no adverse effect on glucose metabolism. Conversely, both drugs seem to improve insulin sensitivity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Body Composition; Body Height; Body Weight; Calcium Channel Blockers; Calorimetry, Indirect; Diabetes Mellitus, Type 2; Dihydropyridines; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Lisinopril; Male; Middle Aged

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).

Topics: Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cholesterol; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nifedipine; Triglycerides

Diabetes mellitus is often associated with hypertension and is an additional cardiovascular risk factor. It is therefore important that antihypertensive drugs should have no negative metabolic effects. We present here the results of two distinct studies investigating the clinical efficacy and the metabolic effects of lacidipine in hypertensive patients without concomitant diabetes. Patients in the first study (group A) were hypertensive with non-insulin-dependent diabetes mellitus (NIDDM) and stable blood glucose levels in the 3 months before entering the study. Patients in the second study (group B) were hypertensive without diabetes mellitus. Before the commencement of the study, antihypertensive treatment was discontinued in all patients for a 4-week washout period, followed by 4 weeks of run-in with placebo. Patients were then treated with lacidipine (4 mg o.d.) for 6 months. After 1-2 months, the dose was doubled in patients with uncontrolled blood pressure. Every 2 months, lipid and carbohydrate metabolism were investigated by blood chemistry analyses. The results demonstrate that lacidipine 4-8 mg o.d. is efficacious and well tolerated in hypertensive patients, even in the presence of diabetes mellitus.

Topics: Adult; Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Female; Humans; Hypertension; Lipids; Male; Middle Aged