Telmisartan and Losartan in Hypertensive IGT

Telmisartan vs. Losartan in Hypertensive Patients With Impaired Glucose Tolerance: A Comparison of Their Antihypertensive, Metabolic, and Vascular Effects

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: Telmisartan 80 mg; Drug: Losartan 50 mg

Detailed 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 Type: Interventional
• Enrollment: 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• IGT according the criteria of the WHO
• standardised office blood pressure > 140/90 mmHG or treated hypertension
• 40 - 75 years of age
• signed informed consent

Exclusion Criteria:

• known hypersensitivity towards telmisartan or losartan
• concommitant treatment with ACE-inhibitors
• BMI > 35 kg/m2
• inability to perform self-control of blood pressure
• acute coronary syndrome or cerebrovascular event within the last 3 months
• Revascularisation within the last 3 months
• heart failure > NYHA 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
HOMA index
ISI
FMD
Blood pressure surge in the morning

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Thomas C. Wascher, MD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Study Completion: June 1, 2006

Study Registration Dates

• First Submitted: December 4, 2006
• First Submitted That Met QC Criteria: December 4, 2006
• First Posted (Estimate): December 5, 2006

Study Record Updates

• Last Update Posted (Estimate): December 5, 2006
• Last Update Submitted That Met QC Criteria: December 4, 2006
• Last Verified: December 1, 2006

More Information

Terms related to this study

• Keywords: endothelial dysfunction; insulin resistance; beta cell function
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan; Telmisartan
• Other Study ID Numbers: TCW-02-04