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A novel dual PPAR-γ agonist/sEH inhibitor treats diabetic complications in a rat model of type 2 diabetes – published online 21/07/2018

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by Md Abdul Hye Khan, Lauren Kolb, Melissa Skibba, Markus Hartmann, René Blöcher, Ewgenij Proschak, John D. Imig

Despite significant progress in diabetes management, approximately 50% of people with type 2 diabetes fail to achieve therapeutic goals. Consequently, rates of diabetes-associated morbidity and mortality are high, mainly due to complications such as cardiovascular, liver and kidney disease. Poor clinical outcomes with current therapies for diabetes are associated with their lack of ability to simultaneously lower blood glucose and treat comorbidities. Consequently, the majority of patients with type 2 diabetes with a comorbid condition require a multi-drug approach to treatment. In this issue, Hye Khan et al (https://doi.org/10.1007/s00125-018-4685-0) report data from a study in which they developed a novel dual-acting molecule, RB394, that concurrently acts as an inhibitor of soluble epoxide hydrolase (sEH) and an activator of peroxisome proliferator-activated receptor-γ (PPAR-γ). In rat models of the metabolic syndrome and type 2 diabetes, which are associated with comorbid cardiovascular, liver and kidney disease, the authors demonstrated that RB394 not only ameliorated type 2 diabetes and its comorbid conditions, but also treated multiple diabetic complications, including diabetic nephropathy and liver injury. The authors conclude that RB394 is a promising molecule with the potential for development into a therapeutic agent for the metabolic syndrome, type 2 diabetes and associated complications.

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