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Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial – published online 11/07/2018

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by Joseph Proietto, Jaret Malloy, Dongliang Zhuang, Mark Arya, Neale D. Cohen, Ferdinandus J. de Looze, Christopher Gilfillan, Paul Griffin, Stephen Hall, Thomas Nathow, Geoffrey S. Oldfield, David N. O’Neal, Adam Roberts, Bronwyn G. A. Stuckey, Dennis Yue, Kristin Taylor, Dennis Kim

Animal and human studies indicate a beneficial effect of methionine aminopeptidase 2 (MetAP2) inhibitors on glycaemic control and other metabolic markers. In this issue, Proietto et al ( report results from the first study of the effects of the MetAP2 inhibitor beloranib in individuals with type 2 diabetes and obesity. The clinical trial was stopped early due to an unexpected imbalance in venous thromboembolism events in beloranib-treated vs placebo-treated individuals across beloranib clinical trials, during late-stage development of the drug. However, in individuals who had completed 26 weeks of treatment, beloranib produced statistically significant placebo-corrected reductions in both HbA1c (−15.3 mmol/mol [−1.4%]) and body weight (−10%). The authors conclude that these data exemplify MetAP2 inhibition as a novel treatment for metabolic disease. Since this trial, a next-generation MetAP2 inhibitor with an improved safety profile has been developed and has shown encouraging efficacy and safety in an ongoing Phase 2 clinical trial in individuals with type 2 diabetes and obesity.

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