Telmisartan and Losartan in Hypertensive IGT
Condition: Hypertension; Impaired Glucose Tolerance
MeSH terms: Glucose Intolerance
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Telmisartan 80 mg; Losartan 50 mg
Intervention type(s): Drug; Drug
Intervention MeSH terms: Losartan; Telmisartan
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: insulin resistance; beta cell function; endothelial dysfunction