Development of synthetic analogs of a sleeve gastrectomy-induced metabolite as a novel therapy for type 2 diabetes and obesity

New therapies are needed to address the related worldwide epidemics of obesity and type 2 diabetes (T2D). Bariatric surgery is currently the most effective and sustainable treatment for obesity. While weight loss occurs 6 months-1 year following surgery, patients see immediate resolution of their diabetic phenotypes within hours of surgery. This remarkable remission of T2D is maintained for over 7 years, suggesting that the change is durable. We have identified a metabolite whose levels are significantly increased in both mice and humans following surgery and that ameliorates diabetic phenotypes in vivo in an acute mouse model. The goal of this research is to develop analogs of this metabolite as a potential therapy for T2D and obesity.