Studies have been conducted in recent years regarding gut hormones and their role in regulating food intake. A review done by professors at the Imperial College of London, Department of Investigative Medicine, focuses on these hormones and the potential to make new gut hormone based obesity treatments.
Researchers working with weight loss surgery patients discovered that gut hormones became altered in post operative patients who had a Roux-en-Y gastric bypass (RYGB) as opposed to those who had a gastric banding procedure. The patients with the RYGB lost more weight and resolved their diabetes more quickly than those with the banding procedure. It is believed that this is due to the hormone changes.
The hormones being studied are glucagon-like peptide-1 (GLP-1), oxyntomodulin, peptide YY, cholecystokinin, pancreatic polypeptide, amylin, and ghrelin. All of these hormones play a role in satiety, or feeling full. They have been studied using both laboratory animals and human subjects with mostly positive results. The most frequent side effect of these hormone therapies is nausea.
GLP-1 has been receiving the most attention as it has proven to be the most responsive for drug development so far. This hormone is released rapidly after eating, in proportion to food intake. In human trials, intravenous infusion reduced the number of calories consumed at the meal immediately following. Patients with Type 2 diabetes mellitus realized both weight loss and improved glycemic control when given long term subcutaneous infusions of GLP-1.
The role of this hormone on satiety has made it one of the most promising targets for the development of hormone based obesity treatments.
There is currently an available treatment for patients with Type 2 diabetes mellitus that uses an injectable form of this hormone. Patients receive two daily injections which improves their glycemic control and significantly reduces body weight.
Oxyntomodulin is another hormone released in proportion to food consumed. It works to inhibit gastric acid and pancreatic exocrine secretion and it prolongs gastric emptying. These things make you feel full longer and studies have shown that oxyntomodulin increases energy expenditure and causes weight loss in obese volunteers. Wyeth Pharmaceuticals is developing a potential obesity treatment using this hormone.
Peptide YY is secreted with GLP-1 and oxyntomodulin after meals. It is released in proportion to calories consumed and is stimulated by protein more than fat. Peptide YY is thought to be a satiety inducing hormone; however, trials using it as an obesity treatment have stopped after significant problems with nausea and vomiting were discovered.
Amylin is a hormone that is co-secreted with insulin. A form of this hormone, called pramlintide, is currently licensed for use in the USA by Amylin Pharmaceuticals. It is used in conjunction with insulin treatment for patients with both Type 1 and Type 2 diabetes. It has been shown to result in modest weight loss in these patients.
More study is needed on the effects of ghrelin, cholecystokinin, and pancreatic polypeptide on appetite in order to develop obesity treatments with them.
Gut hormone based therapies show promise in the treatment of obesity, but more study is required to understand how each hormone effects satiety and how they work in conjunction with each other. Researchers are working to make treatments that mimic the changes in gut hormones brought on by Roux-en-Y gastric bypass. This could lead to improved weight loss therapies and eliminate the need for surgery and the risks associated with it.
Reference: Benjamin C. T. field, Owais B. Chaudhri, Stephen R. Bloom. Obesity treatment: novel peripheral targets. British Journal of Clinical Pharmacology. 2009;68:6, 830-834
Study can be found at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2009.03522.x/full