Recent progress and future options in the development of GLP-1 receptor agonists for the treatment of diabesity.

The dramatic rise of the twin epidemics, type 2 diabetes and obesity is associated with increased mortality and morbidity worldwide. Based on this global development there is clinical need for anti-diabetic therapies with accompanied weight reduction. From the approved therapies, the injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the only class of agents which are associated with a modest weight reduction. Physiological effects of the gastro-intestinal hormone GLP-1 are improvement of glycemic control as well as a reduction in appetite and food intake. Different approaches are currently under clinical evaluation to optimize the therapeutic potential of GLP-1 RAs directed to once-weekly up to once-monthly administration. The next generation of peptidic co-agonists comprises the activity of GLP-1 plus additional gastro-intestinal hormones with the potential for increased therapeutic benefits compared to GLP-1 RAs.