A new treatment combining two hormones can reduce appetite, according to new research presented today at the Society for Endocrinology annual conference in Harrogate, UK. This early study from an internationally-renowned team at Imperial College London provides 'first in human' evidence that a combined therapy using the hormones glucagon and glucagon-like peptide 1 (GLP-1) may form the basis for a new treatment for obesity and diabetes in the future.
Previous results from in animal studies showed that glucagon/GLP-1 combination might be an effective lead to combat obesity and diabetes. The hormones play key roles in regulating blood sugar. Glucagon works in opposition to insulin, preventing the storage of glucose in fat deposits and the liver, and raising blood sugar levels. GLP-1 stimulates the release of insulin to lower blood sugar and also acts at the brain to reduce appetite.
The research team, led by Professor Stephen Bloom, set out to identify whether glucagon and GLP-1 given in combination might work together to reduce appetite. In this small study, 16 human volunteers were randomly allocated to a sequence of four treatment infusions for 120 minutes, separated by at least three days, each: 1) glucagon, 2) GLP-1, 3) glucagon and GLP-1 in combination and 4) a saline infusion as a control. Double-blind crossover experiments such as these are used across clinical research to reliably identify cause and effect in a series of interventions.
The team provided the subjects with a meal at 90 minutes into each infusion, measured the amount of oxygen consumed, took blood samples to measure blood sugar and metabolic hormone levels, and took readings for pulse, blood pressure and nausea, all both at baseline and during the infusions. This provided data on energy intake (amount of food consumed), energy expenditure (oxygen used), blood sugar control, and the safety of and tolerance to the treatment.
The energy intake during the meal was 1086+/-110.1kcal for the control group vs. 879+/-94.2kcal for the hormone combination group: a significant reduction of 13% (p<0.05) which was also not seen when either hormone was given alone (glucagon: 1086+/-96.9kcal, GLP-1: 1052+/-81.3kcal; p>0.05). A non-significant trend toward increased energy expenditure was also observed in the combination and glucagon-alone groups. The infusions were tolerated safely.
The data show that the promising findings using a glucagon/GLP-1 combination in mice can be replicated in man. Appetite was significantly reduced during the combination treatment compared to the glucagon, GLP-1 alone or saline infusions. The group must now test this glucagon/GLP-1 combination treatment in more people and for longer periods of time to see if the effects can be sustained in the long term.
Professor Stephen Bloom, Head of Division of Diabetes, Endocrinology and Metabolism at Imperial College London said: "The hormones glucagon and GLP-1 are both used by the body to control blood sugar and metabolism, so there is great interest in utilising them to find new treatments for obesity and type 2 diabetes.
"We found that volunteers treated with a glucagon/GLP-1 combination consumed significantly less food. These data replicate our findings in animals, suggesting that a glucagon/GLP-1 combination may be a promising lead from which to develop a new treatment for obesity and diabetes.
"13% is a big reduction in food intake by anyone's standards, but our experiment is only an appetiser. An effective future treatment will need to suppress appetite in the long term, so we next aim to establish whether the effects can be sustained to lead to real weight loss."
- Jaimini Cegla, Rachel Troke, Ben Jones, George Tharakan, Katherine McCullough, Julia Wilde, Chung Thong Lim, Naseem Parvizi, Mohamed Hussein, James Minnion, Joyceline Cuenco, Edward Chambers, Mohammad Ghatei, Tricia Tan, Stephen Bloom. Energy intake following infusion of glucagon and GLP-1: a double-blind crossover study. Endocrine Abstracts, 2013; 1 DOI: 10.1530/endoabs.31.OC4.5
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