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document
The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy . OBJECTIVE 11-Beta-hydroxysteroid dehydrogenase type 1 ( 11betaHSD1 ) converts inactive cortisone into active cortisol , thereby amplifying intracellular glucocorticoid action . The efficacy and safety of the 11betaHSD1 inhibitor INCB13739 were assessed when added to ongoing metformin monotherapy in patients with type 2 diabetes exhibiting inadequate glycemic control ( A1C 7-11 % ) . RESEARCH DESIGN AND METHODS This double-blind placebo-controlled paralleled study randomized 302 patients with type 2 diabetes ( mean A1C 8.3 % ) on metformin monotherapy ( mean 1.5 g/day ) to receive one of five INCB13739 doses or placebo once daily for 12 weeks . The primary end point was the change in A1C at study end . Other end points included changes in fasting glucose , lipids , weight , adverse events , and safety . RESULTS After 12 weeks , 200 mg of INCB13739 resulted in significant reductions in A1C ( -0.6 % ) , fasting plasma glucose ( -24 mg/dl ) , and homeostasis model assessment-insulin resistance ( HOMA-IR ) ( -24 % ) compared with placebo . Total cholesterol , LDL cholesterol , and triglycerides were all significantly decreased in hyperlipidemic patients . Body weight decreased relative to placebo after INCB13739 therapy . A reversible dose-dependent elevation in adrenocorticotrophic hormone , generally within the normal reference range , was observed . Basal cortisol homeostasis , testosterone in men , and free androgen index in women were unchanged by INCB13739 . Adverse events were similar across all treatment groups . CONCLUSIONS INCB13739 added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone . 11BetaHSD1 inhibition offers a new potential approach to control glucose and cardiovascular risk factors in type 2 diabetes .
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Intervention_Pharmacological
INCB13739
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
metformin monotherapy
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Intervention_Pharmacological
INCB13739 doses
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Intervention_Control
placebo
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Outcome_Physical
hyperglycemia
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Outcome_Other
efficacy and safety
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Outcome_Physical
change in A1C at study end
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Outcome_Physical
changes in fasting glucose
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Outcome_Physical
lipids
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Outcome_Physical
weight
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Outcome_Adverse-effects
adverse events
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Outcome_Other
safety
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Outcome_Physical
fasting plasma glucose
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Outcome_Physical
homeostasis model assessment-insulin resistance
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Outcome_Physical
Total cholesterol
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Outcome_Physical
LDL cholesterol
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Outcome_Physical
triglycerides
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Outcome_Physical
Body weight
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Outcome_Physical
adrenocorticotrophic hormone
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Outcome_Physical
Basal cortisol homeostasis
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Outcome_Physical
testosterone in men
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Outcome_Physical
free androgen index in women
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Outcome_Other
efficacious
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Outcome_Other
tolerated
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Outcome_Physical
glucose and cardiovascular risk factors
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Participant_Condition
hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy .
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Participant_Condition
302 patients with type 2 diabetes ( mean A1C 8.3 % ) on metformin monotherapy ( mean 1.5 g/day )