Why Behaviour Change Is Still Essential On Glp-1s

Introduction

Glucagon-like peptide-1 (GLP-1) is a hormone that is produced in the intestines, pancreas, and brain.¹ Like most hormones, it is released into the bloodstream, where it can send signals to specific target tissues and organs.² 

GLP-1 helps regulate various physiological processes in the body. It does this by binding to and activating GLP-1 receptors (GLP-1Rs) that are present on cells, including those in the pancreas, brain, heart and blood vessels. Depending on the target cell, the activation of GLP-1Rs will trigger unique cellular responses.¹ 

One of the biological responses includes promoting pancreatic cells to release insulin for the regulation of blood glucose levels. Due to this, medications that can mimic the actions of GLP-1, known as GLP-1 agonists, have been developed to treat type 2 diabetes. They are typically prescribed for patients who are not responding well to the standard triple therapy. GLP-1 agonists help broaden the range of medications available for type 2 diabetic patients, allowing doctors to prescribe the most effective medication to every individual.¹ 

Interestingly, GLP-1 agonists can also be prescribed for weight management, as they play a crucial role in promoting weight loss.³ GLP-1 agonists are often referred to as the ‘magic bullet’ by physicians and researchers due to their effectiveness for individuals who have struggled to manage type 2 diabetes and lose weight through conventional methods.⁴ But is this drug too good to be true? While it may initiate weight loss, it does not ensure long-term success. In this article, we will explore why behavioural changes remain essential, even when using GLP-1 agonists. Specifically, we will cover the following:

• What are the biological effects of GLP-1 agonists?
• How does a GLP-1 agonist contribute to weight loss? 
• The risk of weight gain after discontinuation
• Behavioural change and the foundation for long-term success
• Support for people struggling to lose weight 

What are the biological effects of GLP-1 agonists? 

GLP-1 agonists induce several different biological effects in the body because they can bind to GLP-1R located in the pancreas, central nervous system (CNS) and cardiovascular system.¹ These biological effects are detailed below.

Pancreas

GLP-1 agonists can lower blood glucose levels by stimulating the release of insulin and inhibiting the secretion of glucagon from the pancreas.¹ How exactly does this lower it? Well, insulin activates cells to absorb glucose from the bloodstream, which in turn helps lower blood glucose levels. In contrast, glucagon raises blood glucose concentration by promoting the breakdown of glycogen (glucose storage molecule) in the liver, thereby releasing glucose into the circulation.⁵

Central nervous system (CNS)

The brainstem serves as a central point of communication between the brain and the gut. While the gut relays information about food intake, the brain responds by sending signals that can either promote or suppress feeding behaviour. Without this signalling pathway, we would lack key sensations, such as stomach rumbles and food cravings that drive us to eat, as well as the feeling of fullness that helps limit food intake. GLP-1 agonists can regulate appetite by interacting with these specific cells located in the brainstem.⁶ 

Cardiovascular system

GLP-1 agonists can bind to cells of the heart and blood vessels (specifically the endothelial cells) to induce several different cardiovascular effects. This includes promoting glucose uptake, which is required to generate energy, thereby helping to improve heart muscle contraction. It can also lower blood pressure by stimulating the endothelial cells that line our blood vessels to produce nitric oxide. This will cause the blood vessels to relax, improving blood flow by reducing resistance and increasing the volume of blood transported.⁷ 

How do GLP-1 agonists contribute to weight loss? 

GLP-1 agonists interact with the CNS in complex ways that contribute to their weight loss effects. One proposed mechanism involves the regulation of stomach wall contractions, which are essential for gastric (stomach) emptying. 

What is the link between gastric emptying and weight loss?

The stomach wall consists of muscles required for digestion and the passing of food to the small intestines, where absorption takes place. Muscular contractions typically require electrical signals to be sent from the brain.⁸ The interaction of GLP-1 agonists with the GLP-1Rs in the brain can cause delays in the emptying of the stomach, which helps amplify the feeling of being full and reduces the motivation to seek food.⁹ 

Risk of weight regain after discontinuation

Weight loss drugs can be beneficial for many individuals who struggle to lose weight through diet and exercise alone. However, it is important to understand that the effects of these drugs are not always permanent. 

Semaglutide, a GLP-1 agonist marketed as Wegovy® in the UK, can only be prescribed for a maximum of 2 years due to concerns about its long-term risks. The question is what happens after individuals stop taking it. Studies on individuals who have taken semaglutide for approximately 15 months have shown:¹⁰ 

• Many individuals will regain weight shortly after experiencing withdrawal symptoms 
• Regain of weight occurred within one year of discontinuing the medication 
• The most significant regain was observed in individuals who lost 20% or more of their body weight through semaglutide

Considering this, GLP-1 agonists should not be viewed as a permanent resolution to weight loss. 

Behavioural change: the foundation for long-term success

Implementing healthy eating habits into our daily lives is essential to continue staying fit even after taking GLP-1 agonists. A recent study has highlighted important behavioural considerations for designing effective and sustainable weight management programmes for long-term success.¹¹ While some weight management programmes can be beneficial for supporting behavioural change, they are not always accessible to everyone. Here are some of the key findings that can be applied more broadly and followed by anyone aiming to improve their health:¹¹

• Exercise for 1 or 2 months before changing your eating habits 
• Have at least 3 moderate exercise sessions per week 
• Establish regular increases in the amount of exercise (e.g. run for one minute longer every session)
• Increase fruit and vegetable intake 
• Strictly follow daily calorie limits to maintain weight 
• Weigh yourself regularly to monitor progress and determine whether adjustments to your diet plan are necessary 
• Recognise that overeating should not be considered to be made up for the next day, to ensure that this behaviour does not persist 
• Recognise that exercising for longer does not mean you can consume more calories 
• Recognise behavioural/psychological triggers to eating so that you can avoid them
• Exercise in social groups to provide motivation and encouragement

Support for people struggling to manage weight 

There are many resources available to support your weight management journey. If you are finding it difficult to make progress, consider speaking to your GP, who can refer you to a specialist weight management clinic. The NHS also offers a free, 12-week weight management programme that is accessible for individuals who are over 18, have a BMI over 30 and have diabetes or high blood pressure. If tracking your food intake is helpful for you, the NHS also provides a calorie-counting app that may help.

Remember, while weight management can benefit your physical health, it can also impact your mental well-being, especially if you have a history of eating disorders. Remember to be kind to yourself throughout the process, and do not hesitate to seek support. If you need urgent help, there are helplines available to assist you.

FAQs

Does the NHS provide GLP-1 agonists? 

Wegovy® or Saxenda® are marketed GLP-1 agonists that can be prescribed within a specialist weight management service provided by the NHS.

What is the difference between Wegovy® and Saxenda®? 

Wegovy® is the medication containing semaglutide, whilst Saxenda® contains liraglutide. Semaglutide is more effective than liraglutide largely due to its structural differences.¹²

What are the adverse effects of GLP-1 agonists? 

The most commonly reported side effects were gastrointestinal, including nausea, diarrhoea, vomiting, constipation, and abdominal pain.¹³

Summary

GLP-1 agonists have emerged as effective tools for managing type 2 diabetes and supporting weight loss. By mimicking a natural hormone involved in appetite regulation and blood sugar control, these medications can lead to significant short-term improvements. However, their benefits are not permanent and often diminish once treatment is stopped. This article explains why behaviour change, such as improving diet, increasing physical activity, and addressing emotional eating, remains critical even when taking GLP-1 agonists. Without these foundational changes, long-term weight maintenance is difficult to achieve. Therefore, it is important to combine medication with sustainable lifestyle habits to have the best chance for lasting success.