How do GLP-1 side effects compare between treatments?

If you’re researching GLP-1 treatments like Wegovy or Mounjaro, you’ve probably heard about the impressive weight loss results — and the not-so-fun side effects that can come with them.

Many people experience nausea, changes in appetite, or stomach discomfort when they first start a GLP-1. For some, these symptoms ease within a few weeks. For others, they linger. That’s often when people start wondering: Would I tolerate a different treatment better?

In this article, we’ll explain why GLP-1 side effects happen, how they can differ between medicines, and what you can do to manage them.

A quick recap: how GLP-1s work

GLP-1 medicines mimic a natural hormone called glucagon-like peptide-1, or GLP-1 for short. This hormone helps regulate appetite, digestion, and blood sugar.

When you take a GLP-1 medicine, it binds to the same receptors in the brain and gut as the natural GLP-1 hormone, triggering the same processes in the body. It slows down digestion, helps you feel fuller for longer, and balances hunger signals in the brain. It also supports your body’s ability to release insulin after eating.

These actions make GLP-1s highly effective for weight management, as you eat less and gradually lose weight. But they also explain why some people feel nausea, bloating, or other digestive changes. Your gut and brain are adjusting to a new rhythm, and that can feel rather uncomfortable at first.

Common GLP-1 side effects

Almost all GLP-1 treatments share similar side effects. Most are mild to moderate and tend to improve as your body adapts. The most commonly reported affect your GI tract and include (1):

• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Bloating or stomach discomfort

These side effects are dose-related, which means they’re more likely to occur (or feel stronger) when you first start treatment with a GLP-1 or move up to a higher dose. That’s why doctors usually start low and increase slowly, giving your body time to adapt to reduce these unwanted effects.

How side effects compare between GLP-1 treatments

You might assume that because all GLP-1 medicines work in a similar way, their side effects would be identical. But in practice, that’s not always the case.

Each treatment interacts with your body slightly differently, from how strongly it binds to GLP-1 receptors to how long it stays active in your system. These small differences can subtly influence how noticeable (or tolerable) certain side effects feel.

Let’s take a closer look at the side effects of the main GLP-1s prescribed for weight loss:

Liraglutide (Saxenda)

Liraglutide was one of the first GLP-1s used for weight loss. It’s injected daily rather than weekly, which means hormone levels rise and fall more evenly, and side effects may be milder (2). Nausea, diarrhoea, and constipation are the most common, especially in the first couple of weeks.

Because the dose is increased to its full strength over a few weeks (rather than months), side effects can appear sooner, but some people find they settle more quickly once the body adjusts.

Semaglutide (Wegovy)

Semaglutide is a once-weekly injection that mimics the GLP-1 hormone only. It’s more potent and longer-acting than liraglutide, which often means stronger effects on appetite and generally leads to greater weight loss. Unfortunately, this and sometimes stronger side effects too (2).

Nausea, diarrhoea, and vomiting are the most frequent, particularly during dose increases. These usually improve over time as your body adapts to the slower digestion and altered hunger signals.

Tirzepatide (Mounjaro)

Tirzepatide is the newest of the three GLP-1 weight loss injections and works slightly differently. It mimics not one but two natural hormones: GLP-1 and GIP. This “dual action” helps regulate appetite and blood sugar more broadly, and it may make the medicine more tolerable for some people.

One theory is that GIP activation lowers stomach acid secretion, which could calm the gut a little during adjustment and make Mounjaro side effects less intense.

Which GLP-1 has the fewest side effects?

In a review that looked at the results from many clinical trials on weight loss medications, around 80% of participants taking liraglutide reported some kind of side effects, compared to 90% for semaglutide and 79% for tirzepatide (2). For all three drugs, were mostly mild-to-moderate and short-lived, and the majority were some kind of digestive upset.

Based on these numbers, Mounjaro is “best” in terms of side effects. But it’s important to note that:

1. The total side effects are similar for all three drugs
2. These are broad trends, not hard rules

Everyone’s body chemistry is different, so there’s no single “better tolerated” option. There is only what suits you. Some people feel best on semaglutide, while others prefer tirzepatide. The right option depends on how your body responds.

When side effects are likely to happen

Regardless of which GLP-1 we’re talking about, most people experience side effects:

• When starting treatment, as your body adapts to GLP-1 activity
• After a dose increase, since higher levels can intensify gut effects
• If eating large or high-fat meals, which can trigger nausea or bloating

Small lifestyle tweaks can make a big difference in comfort (3). Try smaller meals, stick to non-greasy, lower-fat foods, and stay hydrated, especially if you’re experiencing nausea or diarrhoea. Some people also find that eating bland foods (like crackers or rice) or sipping ginger or peppermint tea helps settle the stomach.

If nausea or bloating feels unmanageable, or you’re losing weight too quickly, speak to your doctor. They can pause your dose increase or recommend strategies to help.

When to speak to a doctor

Mild digestive symptoms should be expected when starting weight loss drugs and usually ease over time. But you should always contact a healthcare professional if you experience:

• Persistent vomiting or diarrhoea
• Signs of dehydration (such as dizziness or dark urine)
• Severe stomach pain or tenderness
• Any side effects that make it hard to eat or drink normally

Your doctor can check whether your symptoms are typical, or changing the dose or switching to another weight loss medicine might suit you better.

If you’re struggling or unsure which treatment might suit you best, you don’t need to do the guess work alone. At Oxford Online Pharmacy, our UK-registered doctors can help you find a weight loss treatment plan that fits your body, lifestyle, and goals.

References

1. MHRA. GLP-1 receptor agonists: reminder of the potential side effects and to be aware of the potential for misuse [Internet]. GOV.UK. 2024.
2. Ghusn W, Hurtado MD. Glucagon-like Receptor-1 agonists for obesity: Weight loss outcomes, tolerability, side effects, and risks. Obesity Pillars. 2024 Dec;12:100127.
3. Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, Castro A, Cebrián-Cuenca A, de Torres-Sánchez A, et al. Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus. Journal of Clinical Medicine [Internet]. 2023 Jan 1;12(1):145.