Co-infusion of low-dose glucagon-like peptide-1 (GLP-1) and glucagon in man results in a reduction in food intake

Abstract

Obesity is a growing epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side-effects. Both glucagon and glucagon-like peptide 1 (GLP-1) reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. We hypothesised that the combination of both peptides, administered at doses that are individually sub-anorectic, would reduce appetite, while GLP-1 would protect against the hyperglycaemic effect of glucagon.

In this double-blind crossover study, sub-anorectic doses of each peptide alone, both peptides in combination, or placebo, were infused into 13 human volunteers for 120 minutes. An ad libitum meal was provided after 90 minutes and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during infusion.

Glucagon or GLP-1, given individually at sub-anorectic doses, did not significantly reduce food intake. Co-infusion at the same doses led to a significant reduction in food intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycaemia and an increase in energy expenditure of 53 kcal/day was seen on co-infusion. These observations support the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity and diabetes.

Footnotes

  • * J.C and R.C.T contributed equally to this study

  • Received February 12, 2014.
  • Accepted June 12, 2014.

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