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Telmisartan and Losartan in Hypertensive IGT

2014-08-27 03:41:15 | BioPortfolio

Summary

Inhibition of RAS delays onset of diabetes in clinical studies. Preliminary evidence suggests that telmisartan may have unique metabolic properties compared to other ARB due to activation of PPARγ.

This should be tested in comparison with an ARB that is metabolically neutral in already published studies.

H0: Telmisartan is not different from Losartan with respect to metabolic and vascular effects.

H1: Telmisartan is different from Losartan with respect to metabolic and vascular effects.

Description

Background: Both, ACE-inhibitors as well as angiotensin-II-type-1 (AT1) receptor antagonists seem to reduce the development of type-II diabetes in patients with hypertension and/or high vascular risk (1-3). The major drawback of that evidence is that it derives from post-hoc analyses in studies with rather poor metabolic phenotypisation of the populations included. Additionally, all that evidence is based on measurements of fasting plasma glucose.

In subjects with impaired glucose tolerance (IGT), insulin resistance and dysfunction of pancreatic beta-cells (in variable contribution) have already established increased postprandial hyperglycemia with a consecutively increased cardiovascular risk (4, 5). In addition they have a considerable risk for future development of manifest type-II diabetes in the range of 3-6 % within a year (6, 7). In such patients prevention of diabetes may also result in cardiovascular prevention. As subjects with IGT often exhibit a more or less pronounced metabolic syndrome, hypertension is a frequently found comorbidity and vice versa IGT is frequent in hypertensive patients suggesting a possible common soil of the two diseases (8).

Given these evidences, hypertensive subjects with IGT are a very suitable target population to study metabolic and vascular effects of an angiotensin-II-type-1-receptor antagonist.

Finally, it has to be acknowledged that insulin resistance needs to be seen in the context of the proinflammatory changes of the metabolic syndrome, the endothelial dysfunction associated and the possibly central role of the adipocyte (Fig. 1). Within that context, the hypothesis was put forward that blockade of the angiotensin system might prevent type-II diabetes via effects on fat cells (9).

Rationale: The effects of different angiotensin-II-type-1-receptor antagonists on insulin sensitivity have been investigated in various studies with different, either positive (10) or negative (11, 12) results but no in-depht investigations into detailed metabolic and vascular effects have been performed.

Telmisartan is an angiotensin-II-type-1-receptor antagonist that very recently has been described to possess the specific properties of a partial activator of PPARγ (13). This effect is not found for other comparable compunds such as losartan. Genes of whom the expression is under control of that receptor are centrally involved into the pathology of the metabolic syndrome as outlined above and activation of that receptor results in improved insulin sensitivity, ameliorated endothelial dysfunction, reduced inflammation and potentially preserved beta-cell function (for review see (14)). Therefore, telmisartan is a candidate that might possess very specific beneficial properties in addition to its antihypertensive effects.

Objective: To compare the metabolic and vascular effects of telmisartan and metoprolol in hypertensive patients with IGT.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Conditions

Hypertension

Intervention

Telmisartan 80 mg, Losartan 50 mg

Location

Medical University of Graz
Graz
Austria
8036

Status

Completed

Source

Medical University of Graz

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:41:15-0400

Clinical Trials [1172 Associated Clinical Trials listed on BioPortfolio]

PROBE Parallel 6-Week Treatment Comparing Telmisartan/Hydrochlorothiazide (HCT) (40/12.5 or 80/12.5) With Losartan/HCT (50/12.5) Using Ambulatory Blood Pressure Monitoring (ABPM)

To demonstrate that Telmisartan combined with Hydrochlorothiazide (MICARDIS® HCT) is superior to Losartan with Hydrochlorothiazide (Hyzaar®) in lowering blood pressure in mild-moderate h...

Non-responder Study to Telmisartan 40 mg

The objective of this trial is to demonstrate that the fixed dose combination of telmisartan 40 mg and HCTZ 12.5 mg is superior to the monocomponent of telmisartan (Micardis, Gliosartan, K...

Trial of Telmisartan 80 mg/HCTZ 12.5 mg and Telmisartan 40 mg/HCTZ 12.5 mg in Patients With Hypertension

The objective of this trial is to assess the safety and efficacy of 52 weeks of open-label treatment with the fixed dose combination of telmisartan 80 mg plus HCTZ 12.5 mg and telmisartan ...

Filtered Trial for Telmisartan 40mg Non-responder

The primary purpose of this study is to: Demonstrate that a fixed-dose combination of telmisartan 40 mg plus amlodipine 5 mg is superior to telmisartan 40 mg alone in patients with essent...

Combination of Telmisartan 80 mg Plus Hydrochlorothiazide 12.5 mg to Telmisartan 80 mg in Patients Failed in Telmisartan 80 mg

To demonstrate that a fixed dose combination of telmisartan 80 mg plus HCTZ 12.5 mg is superior to telmisartan 80 mg alone in patients, who fail to respond adequately to telmisartan 80 mg ...

PubMed Articles [2010 Associated PubMed Articles listed on BioPortfolio]

A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension.

The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. ...

Direct renin inhibition is not enough to prevent reactive oxygen species generation and vascular dysfunction in renovascular hypertension.

Renin-angiotensin system activation promotes oxidative stress and endothelial dysfunction. However, no previous study has examined the effects of the renin inhibitior aliskiren, either alone or combin...

A Randomized, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and the Tolerability of a Triple Combination of Amlodipine/Losartan/Rosuvastatin in Patients With Comorbid Essential Hypertension and Hyperlipidemia.

The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia.

Losartan suppresses the kainate-induced changes of angiotensin AT1 receptor expression in a model of comorbid hypertension and epilepsy.

Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the change...

Assessment of preclinical pharmacokinetics and acute toxicity of pioglitazone and telmisartan combination.

The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cho...

Medical and Biotech [MESH] Definitions

An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.

A condition in pregnant women with elevated systolic (>140 mm Hg) and diastolic (>90 mm Hg) blood pressure on at least two occasions 6 h apart. HYPERTENSION complicates 8-10% of all pregnancies, generally after 20 weeks of gestation. Gestational hypertension can be divided into several broad categories according to the complexity and associated symptoms, such as EDEMA; PROTEINURIA; SEIZURES; abnormalities in BLOOD COAGULATION and liver functions.

Hypertension due to RENAL ARTERY OBSTRUCTION or compression.

Increased pressure within the cranial vault. This may result from several conditions, including HYDROCEPHALUS; BRAIN EDEMA; intracranial masses; severe systemic HYPERTENSION; PSEUDOTUMOR CEREBRI; and other disorders.

Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.

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