The Rise of GLP-1s 

1st October 2025

By Mia Turner, Scientific Communications and PR Intern.

Glucagon-Like Peptide-1 receptor agonists, or GLP-1 RAs for short, are a class of drugs that were originally developed with diabetes management in mind due to their ability to regulate blood sugar levels and manage metabolism in affected individuals [1]. They’ve also seen broader and widespread applications as weight loss drugs.  

It’s important to note that GLP-1 RAs are far from the first drug line created for management of weight or diabetes. However, they are the class that has been shown to have the most success – with some patients reporting up to 20% body weight loss after a course of the most recent GLP-1 RA treatments [2]. As such, using medications as an alternative to weight loss surgeries is becoming more common, with more medical professionals recommending this course of treatment and popularity growing throughout society.  

What are GLP-1 RAs, and how do they work?  

GLP-1 RAs are proving to be a popular option amongst many looking for an alternative weight loss solution. They’re effective, becoming increasingly accessible and are easy to use through weekly injections. But what actually happens when a GLP-1 RA is injected? 

As a drug, they mimic the natural hormone (GLP-1) that acts to control appetite and food intake by binding to receptors in the brain and pancreas and causing activation of several related pathways. This enhances glucose-dependent insulin secretion, inhibits glucagon release and slows gastric emptying – all actions that work towards reducing appetite and controlling food intake [3].  

The natural regulation of feeding can be categorised into two different types – homeostatic and non-homeostatic. Put simply, homeostatic feeding ensures stabilisation of energy stores in the body while non-homeostatic feeding is driven by the pleasurable properties of food, meaning that it can result in overeating [3].  

In the brain, the brainstem and hypothalamus help to regulate homeostatic feeding by receiving, conveying and integrating peripheral signals from the gastrointestinal (GI) tract about nutrient intake.  

In the nucleus tractus solitarii (NTS), found within the brainstem, GLP-1 RAs bind to GLP-1 receptors and enhance the activity of a particular group of neurones called serotonergic neurones (utilise serotonin), promoting a strong feeling of ‘fullness’ so there isn’t a physiological desire to eat [4]. Serotonin is relevant to the feeling of fullness as it is heavily linked to the reward system of eating. Therefore, by binding to GLP-1 receptors and enhancing the serotonergic neurones, GLP-1 RAs promote this feeling without the associated consumption of highly caloric foods that would contribute to excessive weight gain. 

The area postrema plays a vital role in the vomiting reflex and acts as a sensory motor. It also crucially plays a role in appetite regulation [5]. More specifically, it’s able to discern activation of GLP-1 receptors in this region which can reduce the reward of food intake and further suppress appetite preventing excessive food intake and positively contributing to the effects of GLP-1 RAs. 

GLP-1 RAs also affect the paraventricular nucleus and lateral hypothalamus, increasing release of hormones that reduce food intake and inhibiting those that stimulate appetite, respectively. In a slightly different but related way, GLP-1 receptors that are activated in the mesolimbic reward pathway diminish the reward sensation associated with food – this decreases the motivation to consume foods that are highly calorific and palatable. It can also influence serotonin levels here, which are further associated with both satiety and mood [3].  

The broad effects of GLP-1 RAs on various areas of the brain and hormones associated with feeding all drive towards a lessened appetite and less rewarding motivation to consume more food, pointing towards a clear benefit in weight management – and also preventing blood glucose spikes for those with diabetes.  

Where can GLP-1 RAs be used in practice? 

There are currently three GLP-1 RAs approved for chronic weight management: liraglutide, semaglutide and tirzepatide. Each of these have slightly different mechanisms, but all demonstrate strong efficacy in both blood glucose management and weight management [6].  

Particularly, tirzepatide is a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonist, both marketed by Eli Lilly as Mounjaro for Type 2 diabetes and Zepbound for weight loss [7]. Drugs such as this target multiple receptors, which allows for simultaneous activation of different pathways contributing to appetite management and control of metabolism. This more comprehensive approach to weight management is more effective than just a single agonist, making them a very popular topic for ongoing research to determine what more potential they may have.  

How useful are they? 

Beyond the immediate beneficial effects of GLP-1 RAs, there are more broad positive effects on the whole body. As a by-product of their use in helping with obesity or diabetes, GLP-1 RAs are also recommended for mitigating cardiovascular risk as they lower the chances of cardiovascular events. They also show promise in decreasing the progression of chronic kidney disease, further demonstrating how GLP-1 RAs can have such broad applications beyond traditionally considered diabetic or weight loss management [8]. 

Side Effects & Considerations 

While there are many benefits to GLP-1 drugs, there are also some known side effects of varying severity, depending on the individual.  

Since one of the main ways that GLP-1 RAs cause appetite suppression and increase the time taken for food to pass through the body, common side effects include nausea, diarrhoea and others [2]. There are ways that these side effects can be managed such as through diet modifications to manage the GI side effects – but overall, the medication aspect should always be managed by a doctor. 

A particularly well-known side effect is often colloquially referenced as ‘Ozempic face’, which is rather misleading since it can come as a result of any rapid weight loss, and not just that which is induced medically [6]. Other more serious side effects include pancreatitis, gallstone attacks and bowel obstructions – which require medical intervention.  

Summary

GLP-1 RAs have long been a popular line of treatment for those with diabetes, but have also seen increasingly population applications in weight management. As well as the developments that have been made for its use in these fields, there are also many others that are being made for its broader applications in treatment of other conditions. 

There are many side effects and considerations that need to be taken into account when considering use of these medications, however the promise they show in treatment is a strong indication of the broader applications they can have in the future

References 

1. Decoding the Buzz Around Weight-loss Medications: Unpacking the Revolution of GLP-1 Medications [Internet]. https://www.iqvia.com/blogs/2024/03/decoding-the-buzz-around-weight-loss-medications. 2024. Available from: https://www.iqvia.com/blogs/2024/03/decoding-the-buzz-around-weight-loss-medications 

2. University Hospitals. More Than Weight Loss: How GLP-1 Drugs Help Your Whole Body [Internet]. Uhhospitals.org. 2025. Available from: https://www.uhhospitals.org/blog/articles/2025/04/how-glp-1-drugs-help-your-whole-body 

3. Moiz A, Filion KB, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. Mechanisms of GLP-1 receptor agonist-induced weight loss: A review of central and peripheral pathways in appetite and energy regulation. The American Journal of Medicine [Internet]. 2025 Jan 31;138(6). Available from: https://www.sciencedirect.com/science/article/pii/S0002934325000592?via%3Dihub 

4. Serotonergic – an overview | ScienceDirect Topics [Internet]. www.sciencedirect.com. Available from: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/serotonergic 

5. Mirza M, M Das J. Neuroanatomy, Area Postrema [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544249/ 

6. Catanese L. GLP-1 diabetes and weight-loss drug side effects: [Internet]. Harvard Health. 2024. Available from: https://www.health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more 

7. https://www.facebook.com/Drugscom. Zepbound Vs Mounjaro: Complete Comparison Guide for Weight Loss and Diabetes Treatment [Internet]. Drugs.com. 2025. Available from: https://www.drugs.com/medical-answers/zepbound-mounjaro-complete-comparison-guide-3578880/ 

8. Collins L, Costello RA. Glucagon-like peptide-1 receptor agonists [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/