Solving obesity? A new view on an old problem
The medical world has become increasingly aware that obesity is a complex disease, and that a variety of diets and exercise programs alone are not going to be the solution for everyone with obesity.
Indeed, what has become more apparent, is that the condition arises because of a complex multifactorial interplay including genetics, food environment and neurohormonal factors
So, the old advice about eating less and exercising more has been far too simplistic a solution to what is being recognised as a nuanced and individual problem.
Looking at the role of Glucagon like peptide-1 (GLP-1)
GLP-1 is a peptide hormone which is 30/31 amino acids long. This is triggered in the gut and brain by food calories and interacts with the GLP-1 receptor (GLP-1R). Together they participate in the regulation of what is called “glucose homeostasis”
Glucose homeostasis refers to the management of the ingestion, production, utilisation and storage of blood glucose in the body. It involves your gastrointestinal tracts, your pancreas, your liver, your adrenal glands and your brain as well as your muscles and body fat.
This management of the required balance is critical, for most people we would not want the glucose level less than 4.0 mmol/L
When blood glucose (sugar) levels are too high this is known as Hyperglycaemia, (“Hyper”) and when they are too low it is known as Hypoglycaemia (“Hypo”). Both of these conditions can result in adverse health consequences – which if left untreated can be severe or fatal
It was recently discovered that GLP-1 has a role beyond that of glucose homeostasis. It is best described as a “neuropeptide with physiologically and pharmacologically relevant effects on food intake and body weight, and potential neuro-modulatory roles”.
This means that it is a chemical made up of small chains of amino acids that are synthesised and released by neurons, and which can affect the transmission of a nerve impulse connected with a feedback mechanism which is designed to optimise the digestion and absorption of nutrients.
What are GLP-1 receptor agonists and why are they important?
Originally created to treat diabetes, GLP-1 agonists mimic the effect of GLP-1 but in a way that can be controlled. There are 5 GLP receptor agonists are currently approved here in the UK. These are:
- Exenatide
- Liraglutide
- Lixisenatide
- Dulaglutide
- Semaglutide
Of these Semaglutide has been shown to be the most effective in helping people with intractable weight gain sometimes when administered in a higher dose than when used for the treatment of diabetes.
A randomised double-blind trial people on Semaglutide showed a 15% weight loss in 68 weeks compared to a 2.4% weight loss for those treated with placebo.
Subsequent trials showed that individual who had been taking Semaglutide on a weekly basis for 2 years lost 16.7% of their bodyweight and sustained this loss. They also significantly improved their metabolic health and significantly reduced their risk of developing type 2 diabetes.
There appeared to be no problems with either safety or tolerability after 2 years which is consistent with the similar preparations which have been on the market since 2005
57% of these people maintained a weight loss which was more than 15% of their body weight and 40% maintained a weight loss which was greater than 20% of their body weight. Since most other weight loss medications – alongside a healthy diet - achieve just 5% of sustained weight loss it looks as if Semaglutide is going to be a significant life-changing medication.
This is not just about weight loss, but also about gaining an improvement in
- Blood pressure
- Inflammatory markers
- Insulin and glucose levels
- Cholesterol levels
- Sleep apnoea problems – which thus reduces long terms cardiovascular risk
Undoubtedly, people treated with Semaglutide are also empowered to make changes in their lifestyle which will additionally reduce their risk of developing chronic disease.
An unresolved issue asked by many people is for how long Semaglutide therapy will need to be continued in the long-term? Current studies suggest that when Semaglutide was withdrawn at two years, 80% of the weight was regained within a year - which confirms the difficulty in achieving sustained weight reduction through lifestyle change alone.
I hope you have found this helpful.
Although every effort is made to ensure that all health advice on this website is accurate and up to date it is for information purposes and should not replace a visit to your doctor or health care professional.
As the advice is general in nature rather than specific to individuals Dr Vanderpump cannot accept any liability for actions arising from its use nor can he be held responsible for the content of any pages referenced by an external link
