Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this investigation. Both have been found to reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. It is proposed that co-administration of both peptides will have an additive effect on appetite reduction, while GLP-1 will protect against the hyperglycaemic effect of glucagon.
In this double-blind crossover study, a weight-adjusted dose of each peptide, alone or in combination, or placebo, was infused into 12 human volunteers for 120 min. An ad libitum meal was provided after 90 min and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during the infusion. At regular time points blood samples were taken for assay of glucose, insulin, GLP-1 and glucagon. Pulse, blood pressure and self-perceived nausea levels were also recorded at each time point.
Co-infusion of glucagon with GLP-1 led to a reduction in food intake of 17.9%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycaemia and a trend of increased energy expenditure was seen on co-infusion of glucagon with GLP-1. This was achieved in the absence of negative effects on cardiovascular parameters.
This study therefore supports the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity.
Declaration of funding
This work was supported by the Wellcome Trust.