Obesity - an indication for GLP-1 treatment? Obesity pathophysiology and GLP-1 treatment potential.

Obesity is common and associated with a high rate of morbidity and mortality; therefore, treatment is of great interest. At present, bariatric surgery is the only truly successful treatment of severe obesity. Mimicking one of the effects of bariatric surgery, namely the increased secretion of glucagon-like peptide (GLP)-1, by artificially increasing the levels of GLP-1 might prove successful as obesity treatment. Recent studies have shown that GLP-1 is a physiological regulator of appetite and food intake. The effect on food intake and satiety is preserved in obese subjects and GLP-1 may therefore have a therapeutic potential. The GLP-1 analogues result in a moderate average weight loss, which is clinically relevant in relation to reducing the risk of type 2 diabetes and cardiovascular disease. Inspired by the hormone profile after gastric bypass, a future strategy in obesity drug development could be to combine several hormones, and thereby produce a superior appetite suppressing hormone profile that may result in a weight loss exceeding that seen in single-agent trials. In conclusion, with the GLP-1 analogues combining a moderate weight loss with beneficial effects on metabolic and cardiovascular risk factors, it seems that we are on the right track for future treatment of obesity.