How GLP-1 Medications Work — And How Wegovy, Mounjaro, and Foundayo Differ

If you have recently been looking into medical weight loss, you will probably have come across the term "GLP-1" – commonly used to reference medications such as Wegovy, Mounjaro, or the recently approved Foundayo. These medications have fundamentally changed what is possible for people trying to manage their weight, but the terminology can be confusing, and it is not always clear how the different medications differ from one another.

This article explains exactly how GLP-1 medications work, what they do to the body, and the practical differences between the treatments currently available in the UK. It is written as a broad guide to what treatments are available – but not a recommendation for specific treatment. This is something that only a qualified clinician can do after fully reviewing your full medical history.

What is a GLP-1 and how do these medications work?

GLP-1 (glucagon-like peptide-1) is a natural hormone that your gut releases after eating. Among other things, it signals to your brain that you're full, and it slows the rate at which your stomach empties itself into your small intestine. This means your body absorbs food at a much slower rate.

GLP-1 receptor agonist medications copy this hormone, but in a far more sustained and pronounced way than your body produces naturally. In practical terms, this essentially means:

• Reduced appetite – many people report feeling fuller, sooner, and for longer after meals.

• Slower gastric emptying – food stays in the stomach longer, which extends the feeling of fullness.

• Better blood sugar regulation – these medications also affect insulin and glucagon release. They were originally developed for the treatment of type 2 diabetes.

Some newer GLP-1 medications go a step further by acting on a second hormone receptor known as gastric inhibitory polypeptide (GIP). This has a further effect on appetite and metabolism.

The main options compared

There are a few important things to note about this table:

• Mounjaro's dual mechanism (acting on both GLP-1 and GIP receptors) is the main pharmacological difference between it and semaglutide-based medications (Wegovy). It is believed this is the reason why it has shown somewhat greater weight loss in clinical trials.

• Foundayo is the newest medication, and it is the first non-peptide (small molecule) GLP-1 medication to be approved in the UK. This means that it does not need to be manufactured in the same way as injectable peptide medications, and it is part of the reason why it is an effective daily tablet.

• The Wegovy pill and Foundayo are both oral medications, but they are chemically distinct (semaglutide vs. orforglipron) rather than two versions of the same drug.

How effective are they?

It is common for patients to ask the question: which GLP-1 medication is best for weight loss? This is not a straightforward question to answer, as the effectiveness depends on the dose and most of the medications have not been tested directly against one another in clinical trials. A summary of the clinical trial results for the highest dose of each medication over a 68–72 week period is set out below:

- Wegovy 2.4mg (STEP-1 trial): around 14.9% average weight loss

- Wegovy 7.2mg (STEP UP trial): around 20.7% average weight loss

- Mounjaro 15mg (SURMOUNT-1 trial): around 20.9% average weight loss

- Foundayo (ATTAIN-1 trial): around 11.2% average weight loss at its highest dose

There are two important things to note with these clinical trial results. Firstly, these were trials with different participants and not head-to-head comparisons. Cross-trial comparisons can give a useful overall picture, but they are not as reliable as two medications tested against one another in the same group of people. Secondly, average trial results always mask individual variation; some participants respond more strongly than the average, and others less so. The response can depend on factors like starting weight, adherence, and individual biology.

What about side effects?

All GLP-1 medications carry similar general side effects, as they all work in a similar way. The most common side effects, particularly when a patient starts their GLP-1 treatment, are gastrointestinal – nausea, mild constipation or diarrhoea, and occasional vomiting. These typically settle down as your body adjusts to the medication. We help our new patients who experience these side effects through the use of anti-nausea medication.

The less common, but more serious, side effects can include gallbladder problems and pancreatitis. The medications are also not suitable for everyone – for example, they are not recommended if you are pregnant or breastfeeding, and there are some specific contraindications relating to thyroid conditions. This is why it is important to undertake a thorough medical assessment, and not just a BMI check, before starting treatment.

Foundayo is a newly licensed medicine and is currently subject to additional monitoring by the Medicines and Healthcare products Regulatory Agency (MHRA). This means that the regulator is gathering more clinical safety data than it would for an established medicine. It does not mean the drug is less safe, but that there is less clinical data available.

Which option might suit you?

This is the most important question, and it is one that can only be answered in consultation with your clinician. There are, however, some practical factors that you can consider now:

• Needle aversion – many people have a fear of needles. If this is something you cannot overcome, then oral GLP-1s (such as the Wegovy pill and Foundayo) are good alternatives.

• Cost – There is a difference in cost between the medications which may affect your decision as to which treatments would be practical for you to start on.

• Routine – Some people find it easier to have a routine of taking a daily tablet, whereas others prefer the "set it and forget it" nature of a weekly injection.

• How your body responds – This genuinely varies from person to person. It is common for your clinician to increase the dose, or even change the medication, if your first choice is not working.