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✍️Ellen Loft ¦ BSc Natural Sciences graduate, University of Leeds
Why are weight loss drugs so important? 💊
Global obesity rates are projected to increase by 13% by 2035.
Today, 38% of the world are overweight or obese. By 2035, this number is expected to rise to over 51%. This will be detrimental to global health and will consume 2.9% of global GDP.
In the background noise of social media gossip and slimming influencers' advice on weight loss, the real information about weight loss drugs is being lost.
Obesity is now regarded as a chronic disease by health professionals and can increase the risk of other diseases such as:
Diabetes
Heart disease
Stroke
Cancer
A new generation of weight loss drugs: how do they work? 💪
Common weight loss drugs mimic the action of GLP-1, a naturally occurring enzyme.
Successful weight loss drugs have been used for over 20 years; the most recent and successful drugs include semaglutide and tirzepatide. These imitate the action of Glucagon-like Peptide-1 (GLP-1).
GLP-1 is an enzyme produced and released from cells in the lining of the intestine. It is released in response to a meal, usually within minutes of eating.
Schematic of GLP-1 hormone being released from intestines
Generated by AI on Wix
Once GLP-1 enters the bloodstream, it binds to complementary receptors on the surface of the pancreas that trigger excess glucose in the blood to be stored as glycogen and insulin to be released. This allows maintenance of a healthy blood glucose level.
GLP-1 binding also has several other effects:
Slowing the emptying of the stomach, prolonging the feeling of fullness and reducing appetite.
Changing fat tissue from white to brown tissue, meaning more fat tissue can be used as an energy source.
💡White fat tissue stores excess energy as large droplets of fat. Brown fat tissue contains smaller fat droplets and can be burned to generate energy and heat.
How were GLP-1 agonists first discovered to aid weight loss?🕵️
GLP-1 agonists were first developed to treat diabetes
Due to their ability to improve glucose regulation, they were originally developed as a treatment for diabetes.
People living with both Type I and Type II Diabetes suffer from insufficient insulin production in the pancreas. Therefore, these drugs that mimic the shape of GLP-1, also known as GLP-1 agonists, increase insulin production and can aid diabetic patients in normalizing their blood glucose, particularly after meals. This can prevent high blood glucose and weight gain.
Which other diseases could these drugs treat?🩸
It is not only diabetes and weight loss that these drugs have the potential to target.
Parkinson's disease
Parkinson's disease causes a progressive loss of motor control over time, predominantly due to the deterioration of dopamine-producing neurones in the brain.
In a clinical trial in 2014 , 78 patients taking a GLP-1 agonist called Lixisenatide showed no worsening of their Parkinson's symptoms over a 12-month period. This is compared to the placebo group, who experienced a worsening in their disability, in line with the usual progression of Parkinson's disease.
However, nausea occurred in almost half the participants taking Lixisenatide, and others experienced vomiting. Larger-scale trials are needed to further assess the efficacy and safety of Lixisenatide , but this study marks a significant step in Parkinson's disease research.
Cancer
One way cancer can affect the body and reduce the immune system's ability to fight tumours is through the reduction of functioning natural killer (NK) cells. Obesity can impede the ability of NK cells to kill tumour cells, therefore increasing risk of cancer progression.
A small study using 20 people with obesity suggested that long-acting GLP-1 drugs could restore NK function over a 6-month period. This result was not associated with weight loss in the trial, suggesting a separate mechanism was occurring. Despite this promising result, this study did not prove reduction of cancer risk, but just a mechanism that can impact tumour progression.
Other studies have shown that GLP-1 agonists could actually increase cancer risk. For example, a 2023 study showed a 58% increase in all types of thyroid cancers in patients who had take GLP-1 agonists for 1-3 years.
These contrasting results demonstrate that rigorous study is needed to identify the true risks and benefits of GLP-1 agonist drugs as a cancer treatment.
Cardiovascular disease
Heart disease is twice more likely in people with Type II Diabetes. This is due to a combination of factors, including their high blood glucose levels and high blood pressure.
One study showed that individuals who had received GLP-1 agonist drugs had a reduced risk of heart failure and major cardiac events leading to hospitalisation. It is not known if the underlying mechanism of these results were from weight loss or improved glucose control. Despite this, these advantageous results for patients with Type II Diabetes are promising in reducing cardiovascular incidences.
What must be considered by stakeholders when using
GLP-1 mimicking drugs in other disease treatment?🧑🤝🧑
The advantages and disadvantages of these drugs must be considered before further use is recommended.
These drugs have a lot of potential benefits for a wide range of patients and diseases. These tend to be cumulative, so the benefits for a patient living with diabetes will also tackle other diseases they may be at risk of, like cardiovascular disorders.
The side effects, including gastrointestinal issues, could be addressed through adjusted doses or additional medication to manage symptoms.
Now, the focus must shift to investigating the long-term efficacy and safety of GLP-1 agonists for non-
diabetic patients. This is because the majority of the current data for these drugs relates to their use for the treatment of diabetes only.
Edited by Zoe Davies | Associate Content Editor | BSc Pharmacology graduate, University of Leeds
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