OBJECTIVE11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone into active cortisol, thereby amplifying intracellular glucocorticoid action. The efficacy and safety of the 11βHSD1 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 METHODSThis 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.RESULTSAfter 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.CONCLUSIONSINCB13739 added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone. 11βHSD1 inhibition offers a new potential approach to control glucose and cardiovascular risk factors in type 2 diabetes.

No abstract

INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.

Topical INCB018424 dosed for 28 days QD or BID is pharmacologically active in patients with active psoriasis and modulates proinflammatory cytokines in the pathogenesis of psoriatic lesions.

Background: Management of acute necrotizing pancreatic infection (ANPI) has changed during last years to less aggressive approach. We present our experience in a tertiary Universitary Hospital. Methods: Retrospectively collected data from consecutive patients (p) with ANPI treated in our Hospital from 2010-2016. Definition of pancreatic infection was established by positive culture of pancreatic and/or peripancreatic necrosis and/or presence of gas in TCscan. We analyze our results according to treatment approach: 1) only antibiotic treatment (ABT), 2) ABT+drainage 3) ABT+drainage+surgery (open or endoscopic) and 4) ABT+open surgery. Variables recorded: Atlanta 2012 classification, hospital stay, mortality, type and mean time to surgery (MTS). Results: Sixty patients had ANPI. Global mortality was 25%. Group1: 14p (2 severe, 12 moderate). Hospital stay 28 days. Mortality 1p. Group2: 13p (4 severe, 9 moderate). Stay 41 days. Mortality 1p. Group3: 14p (9 severe, 5 moderate). Stay 61 days. Mortality 1p. MTS 82 days. 3p were treated endoscopically. 11p open surgey (8 necrosectomies, 2 cystgastrostomies, 1 first necrosectomy and later retropertoneoscopy). Group4: 19p (12 severe, 7 moderate). Stay 32 days. Mortality 12p. MTS 8 days. All were open necrosectomies. Conclusion: Only ABT is effective in selected p. Up to 45% of p can be treated without surgery. Delayed surgery is recommended but in p without organic failure. Patients who needs early surgery still have a high mortality. Treatment should be tailored to p clinical condition.