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Table 6. 11β-HSD1 inhibitors – Strengths, Weaknesses, Opportunities and Threats.

Strengths Weaknesses

z Novel mode of action z Still in the early stages of development
z Orally active z Not yet supported by a large body of late phase
clinical data
z Weight neutral and may even result in weight loss No data on long-term inhibition of 11β-HSD1
z Should improve glycaemia without inducing hypogly- z
caemia z 11β-HSD1 inhibition is an unknown quantity in
T2DM management
z Favourable effects on triglycerides and blood pressure
z Unknown how 11β-HSD1 inhibition could fit in
combination therapy
z 11β-HSD1 also expressed in the CNS
z Concerns over adrenal gland compensation and
activation of the hypothalamic-pituitary-adrenal
(HPA) axis
z Concerns over excess production of adrenal
androgens

Opportunities Threats

z T2DM management is moving beyond simple z Unknown how 11β-HSD1 inhibition may affect
glycaemic parameters lipidaemia in the long-term
z Coverage of all metabolic syndrome characteristics z Emergence of other agents with a more familiar
with one drug mode of action

z The position of many OADs is being eroded by
safety concerns (e.g. SUs, TZDs)
z Some early concerns not borne out in initial human
studies

z Pathway may attenuate progression of T2DM
z May improve CV risk factors

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