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Will treating diabetes with 11β-HSD1 inhibitors affect the HPA axis?

Erika Harno1, Anne White

  • 1Faculties of Life Sciences and Medical and Human Sciences, Manchester, Academic Health Sciences Centre, University of Manchester, UK.

Trends in Endocrinology and Metabolism: TEM
|July 3, 2010
PubMed

Insights

Inhibitors of 11β-HSD1 show promise for type 2 diabetes by reducing tissue cortisol. However, potential impacts on the hypothalamic-pituitary-adrenal (HPA) axis require further detailed investigation.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • 11β-HSD1 inhibitors are investigated for type 2 diabetes treatment.
  • These drugs reduce local cortisol, impacting gluconeogenesis and lipid metabolism.
  • Concerns exist regarding potential hypothalamic-pituitary-adrenal (HPA) axis dysregulation.

Purpose of the Study:

  • To review evidence on 11β-HSD1 inhibition and HPA axis function.
  • To assess the impact of 11β-HSD1 inhibitors on cortisol feedback mechanisms.
  • To identify gaps in understanding HPA axis responses to 11β-HSD1 modulation.

Main Methods:

  • Review of studies involving 11β-HSD1 knockout and transgenic mice.
  • Analysis of data from 11β-HSD1 inhibitor studies.
  • Evaluation of clinical trial results focusing on HPA axis biomarkers.

Main Results:

  • Current analysis of HPA axis biomarkers in clinical trials is often insufficient.
  • Evidence suggests a need for more detailed examination of HPA axis responses.
  • Subtle changes in HPA axis pulsatility, rhythm, and stress response warrant further study.

Conclusions:

  • Further research is needed to fully understand the HPA axis implications of 11β-HSD1 inhibitors.
  • Detailed assessment of HPA axis dynamics, including rhythm and stress, is crucial.
  • Ensuring HPA axis safety is essential for the therapeutic development of 11β-HSD1 inhibitors.

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