Endocrine Abstracts

Obesity is reaching epidemic levels especially in western countries and has become a major public health issue because is frequently associated with other comorbidities such as hypertension, dyslipidemia and diabetes. Therefore, there is increasing interest in the development of therapies against obesity that can offer additional improvements in those associated comorbidities. Unfortunately the current pharmacological treatments have demonstrated limited efficacy, leaving bariatric surgery as the only treatment that promotes a substantial reduction of body weight and in glycemic control. With the aim of establishing new pharmacological alternatives to the use of bariatric surgery, we have developed new single molecules able to activate several hormone receptors involved in the control of energy balance. We have previously proved the efficacy of a peptide with coagonist activity for both glucagon-like peptide-1 (GLP-1) and glucagon receptor, on body weight loss and glycemic control in rats and mice. Now we have designed a novel single peptide coagonist that activates both GLP-1 and glucose-dependent insulinotropic peptide (GIP) receptor. This coagonist is protected from degradation in plasma by dipeptidyl peptidase IV (DPP-IV) and shows a long-lasting activity in rodent models, inducing a greater reduction in body weight and improving glycemic control than other peptides with single agonist activity for the GLP-1 receptor, currently available therapies for the treatment of type 2 diabetes. Our data suggest that the rational design of peptides that can simultaneously modulate the activity of several receptors involved in the control of energy metabolism offers new pharmacological alternatives for the treatment of obesity and diabetes.