eprosartan and Diabetes-Mellitus--Type-2

We evaluated the antihypertensive activity, glucose homeostasis and plasma lipid profile in patients with mild hypertension and type 2 diabetes mellitus treated by diet and exercise, and not in receipt of oral hyperglycemics, following 12-month treatment with either telmisartan or eprosartan. In this double-blind, placebo-controlled trial, 119 patients with mild essential hypertension (diastolic blood pressure [DBP] 91-104 mmHg) and type 2 diabetes were divided into three groups and randomized to receive once-daily telmisartan 40 mg, eprosartan 600 mg, or placebo for 12 months. At enrollment, patients were advised on diet (1,400-1,600 kcal/day) and exercise (physical aerobics on a bicycle for at least 30 min on 4 days each week). Compared with baseline, a significant reduction (p<0.01) in seated trough systolic blood pressure (SBP) was detected after 12-month treatment with either telmisartan or eprosartan. Seated trough DBP was also reduced by telmisartan (p<0.01) and eprosartan (p<0.05); the antihypertensive effect of telmisartan was significantly superior (p<0.05). No change in body mass index or glucose metabolism was observed with either active treatment, or with placebo. Telmisartan, but not eprosartan, significantly improved plasma total cholesterol (p<0.01), low-density lipoprotein cholesterol (p<0.01) and triglycerides (p<0.05) compared with eprosartan. In conclusion, 12-month telmisartan treatment produced a significantly greater reduction in DBP than eprosartan and significantly improved plasma lipids. The improvement could be due to varying pharmacokinetic/pharmacodynamic properties of telmisartan compared with eprosartan, even if it is not clear about the relationship between angiotensin-II receptor blockade and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Benzoates; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Glucose; Homeostasis; Humans; Hypertension; Imidazoles; Lipids; Male; Middle Aged; Telmisartan; Thiophenes

The potential for eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, to affect the 24-hour plasma glucose profiles in type II diabetic patients treated with glyburide was investigated in this randomized, placebo-controlled, double-blind (eprosartan-placebo phase only), two-period, period-balanced, crossover study. All patients received a stable oral dose (3.75-10 mg/day) of glyburide for at least 30 days before the first dose of double-blind study medication was administered. Patients were randomized to receive either 200-mg oral doses of eprosartan twice daily or matching oral placebo doses concomitantly with glyburide for 7 days during each treatment period. After a minimum washout period of 14 days, patients were crossed over to the alternate treatment. Serial samples to measure glucose concentrations in plasma were collected over a 24-hour period on the day before administration of eprosartan or placebo and again on day 7. Mean glucose concentrations were comparable between treatment groups before administration of eprosartan or placebo. The point estimate (90% confidence interval) for the ratio of the average mean 24-hour plasma glucose concentrations of eprosartan + glyburide to placebo + glyburide after 7 days of administration was 0.96 (0.90, 1.01). Eprosartan did not significantly alter the 24-hour plasma glucose profile in patients with type II diabetes mellitus who were previously stabilized on glyburide.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Interactions; Female; Glyburide; Humans; Hypoglycemic Agents; Imidazoles; Male; Middle Aged; Sweating; Thiophenes

Hypertension, a form of cardiovascular diseases, is considered a major risk factor associated with deaths in type 2 diabetes patients. The current medication systems for treating such chronic coexisting diseases are limited and challenging due to the difficulties in overcoming the side effects from complex therapeutic and treatment regimen. The objective of the present study is to design and optimize pioglitazone (PIO) and eprosartan mesylate (EM)-loaded nano-transferosomes (NTs) using Design-Expert software, aiming its transdermal delivery as a novel combination therapy for concomitant treatment of hypertensive diabetic patients. The developed formulations were characterized for various parameters, including in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities. NTs were prepared using PIO and EM as the two model drugs and optimized using Box-Behnken design by considering phospholipid (X1), surfactant (X2), ratio of solvents (X3), and sonication time (X4), as independent variables, each at three levels. Entrapment efficiency (Y1 and Y2) and flux (Y3 and Y4) of PIO and EM, respectively, were selected as dependent variables. Among all the prepared formulations, one optimized formulation was chosen by the point prediction method and evaluated for drug-polymer compatibility, particle size, and surface charge analysis, followed by skin permeation and pharmacodynamic studies. The optimized nano-transferosomal gel (ONTF) showed all responses which confirm with the values predicted by the design. Pharmacodynamic studies showed improved and prolonged management of diabetes and hypertension in Wistar rats after the ONTF was applied, compared to oral and drug-loaded NT formulations. Results of the current study suggest that the development of such combinational delivery system can result in a rational therapeutic regimen for effective treatment of concomitant disease conditions of diabetic hypertensive patients.

Topics: Acrylates; Animals; Diabetes Mellitus, Type 2; Drug Carriers; Drug Delivery Systems; Humans; Hypertension; Imidazoles; Liposomes; Mesylates; Particle Size; Pioglitazone; Rats; Rats, Wistar; Thiophenes

The subjects of the study were 30 patients with type II diabetes mellitus and mild or moderate arterial hypertension. Clinical-and-hemodinamic organoprotective effects of eprosartan, a new angiotensin II blocker, was evaluated in these patients within 16 weeks. The study found a good hypotensive effect of monotherapy with eprosartan in a mean therapeutic dose of 600 mg/day--the target blood pressure levels were achieved in 63.3% of the patients. Fasting insulin level and insulin resistance decreased, which improved hydrocarbonate and lipid exchange parameters. Eprosartan was significantly effective as an organoprotective agent: the patients displayed improvement of eye ground vessel condition, decrease of microalbuminuria, improvement of cardiodynamic parameters i.e. decrease of the thickness of left ventricular (LV) back wall and intravenricular septum, as well as reduction of myocardial mass index. 70% of the patients demonstrated improvement of LV diastolic function.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Diastole; Female; Humans; Hypertension; Imidazoles; Insulin; Insulin Resistance; Lipid Metabolism; Male; Middle Aged; Receptor, Angiotensin, Type 1; Thiophenes; Time Factors; Treatment Outcome; Ventricular Function, Left