What are the most common side effects of GLP-1 Agonists?

By 
Dr Amit Kumar Singh
 on 
Nov 14, 2024
 • 
5
 min read

Starting a GLP-1 medication, such as Wegovy or Mounjaro, brings excitement about its benefits for weight loss and blood sugar management. But as with many effective medications, you might be wondering: What are the side effects, and are they worth it? It’s common to feel a mix of hope and apprehension when beginning a treatment. Recent studies have shown that as many as 30-40% of GLP-1 users experience some level of discomfort from side effects. 

This can feel overwhelming and even a bit frustrating how can a medication designed to support your health cause you to feel worse? Side effects like nausea, vomiting, and indigestion can disrupt your daily routine, sometimes making it hard to see the positives when your body is adjusting. This frustration is common, but it's important to know that you’re not alone in feeling this way, and many people have found ways to successfully manage these issues.

Knowing what to expect and learning about strategies to handle these side effects can significantly improve your experience. Many users discover that with adjustments in dosage, dietary changes, or even temporary medication pauses, the journey becomes smoother. Your health goals, like achieving sustainable weight loss and improved glucose control, are absolutely possible with the right approach to managing these side effects. So, while the road might start out a bit bumpy, a brighter, healthier future can still be within reach, backed by the support and resources available to help you along the way.

How GLP-1 Medications Work

Glucagon-like peptide-1 (GLP-1) medications, also known as GLP-1 receptor agonists, are a class of drugs primarily used to treat type 2 diabetes and obesity. They mimic the action of the natural hormone GLP-1, which is released by the intestines in response to food intake. Understanding how these medications work involves examining their mechanism of action, effects on appetite regulation, blood sugar control, and weight loss.

Mechanism of Action

GLP-1 medications work by activating the GLP-1 receptors in the body. Here are the key actions they perform:

  • Stimulating Insulin Secretion: GLP-1 agonists enhance insulin secretion from pancreatic beta cells in a glucose-dependent manner. This means they stimulate insulin release only when blood sugar levels are elevated, reducing the risk of hypoglycemia (low blood sugar).
  • Inhibiting Glucagon Release: These medications suppress the secretion of glucagon, a hormone that raises blood sugar levels. By inhibiting glucagon, GLP-1 agonists help lower blood sugar levels.
  • Slowing Gastric Emptying: GLP-1 medications delay gastric emptying, which helps to slow down the absorption of nutrients and reduces post-meal blood sugar spikes.
  • Reducing Appetite: By acting on areas of the brain that regulate appetite, GLP-1 agonists promote feelings of fullness (satiety), leading to reduced food intake.

Regulation of Appetite and Weight Loss

The appetite-regulating effects of GLP-1 medications are significant:

  • Satiety and Reduced Food Intake: Clinical studies have shown that patients using GLP-1 agonists experience a decrease in hunger and an increase in feelings of fullness after meals. For example, a critical review of liraglutide ( a similar class drug not approved in the UK) for weight management demonstrated that participants had a significant reduction in calorie intake and body weight compared to those receiving a placebo.
  • Weight Loss Outcomes: Research indicates that GLP-1 agonists can lead to substantial weight loss. In clinical trials, patients treated with these medications lost an average of 5% to 10% of their body weight over several months. For instance, semaglutide has been shown to result in an average weight loss of approximately 15% in obese individuals without diabetes.

Blood Sugar Control

GLP-1 medications play a crucial role in managing blood sugar levels:

  • Clinical Efficacy: A meta-analysis found that GLP-1 receptor agonists significantly reduce HbA1c levels (a measure of long-term blood glucose control) by about 0.8% to 2% compared to placebo treatments. This reduction is clinically meaningful and can improve overall diabetes management.
  • Cardiovascular Benefits: Studies have also indicated that GLP-1 agonists may reduce cardiovascular risks associated with diabetes. For example, liraglutide has been associated with lower rates of cardiovascular events in patients with type 2 diabetes

Common Side Effects of GLP-1 Medications

Gastrointestinal Side Effects

Gastrointestinal issues are the most common side effects associated with GLP-1 medications. These include:

  • Nausea: Up to 50% of patients report experiencing nausea, especially when starting the medication or increasing the dose. This side effect is often transient but can lead to discontinuation in some cases.
  • Vomiting: Alongside nausea, vomiting can occur, particularly in the initial phases of treatment. Patients may need to manage this by staying hydrated and eating smaller, more frequent meals.
  • Diarrhoea: This side effect is also commonly reported, with studies indicating that it can affect a significant percentage of users. Diarrhoea may lead to dehydration and acute kidney injury in severe cases due to volume contraction.
  • Constipation: Some patients experience constipation, which can be managed through dietary adjustments and increased fluid intake.
  • Abdominal Pain: Abdominal discomfort is another potential gastrointestinal side effect. It may be related to the slowing of gastric emptying caused by GLP-1 agonists.

Other Side Effects

In addition to gastrointestinal symptoms, patients may experience other side effects:

  • Fatigue: Some users report feelings of tiredness or fatigue, which can impact daily activities.
  • Headache: Headaches are relatively common among users of GLP-1 medications, although they are generally mild and manageable.
  • Dizziness: Dizziness can occur, particularly when standing up quickly or if dehydration results from gastrointestinal symptoms.
  • Taste Changes: Some patients report alterations in taste perception while on GLP-1 medications, which can affect appetite and food choices.
  • Pancreatitis: Although rare, there have been reports linking GLP-1 medications to pancreatitis. Patients with a history of pancreatitis should not use these medications and should consult a GP before considering.

Managing Side Effects of GLP-1 Medications

Managing the side effects during the initial phase of treatment can really be beneficial for you. It will keep you motivated to continue the GLP-1 agonist treatment. Here are some practical tips and recommendations to manage the side effects:

Starting with a Low Dose and Gradually Increasing

This is found to be really helpful in mitigating the side effects. A study from the SUSTAIN 10 trial showed that starting with a lower dose of semaglutide reduced the incidence of gastrointestinal side effects. Participants who began at a lower dose reported fewer episodes of nausea compared to those who started at the standard dose.

In the UK, Mounjaro (Tirzepatide) is typically initiated at a starting dose of 2.5 mg once a week for four weeks to help the body adjust and reduce gastrointestinal side effects, after which the dose may be gradually increased based on individual tolerance and clinical response, according to guidelines from the National Institute for Health and Care Excellence (NICE). Wegovy (Semaglutide) is similarly started at 0.25 mg weekly for four weeks before gradually increasing, allowing patients to acclimate and minimise side effects like nausea and vomiting (NICE, 2023).

Staying Hydrated

Dehydration can exacerbate side effects like nausea and diarrhoea. A study highlighted that adequate hydration is crucial for patients experiencing gastrointestinal symptoms .

Recommendation: Drinking plenty of fluids throughout the day can help manage these side effects effectively.

Eating Smaller, More Frequent Meals:

Evidence suggests that smaller, more frequent meals can help reduce nausea and improve overall tolerance to GLP-1 medications. A longitudinal assessment noted that patients who adopted this eating pattern experienced fewer gastrointestinal disturbances.

Practical Tip: Instead of three large meals, patients should aim for five to six smaller meals throughout the day to maintain satiety and minimise discomfort.

A close-up of a girl with her eyes closed and a hand on her forehead, visibly distressed by a headache.

When to Seek Medical Advice Regarding GLP-1 Medications

  1. Severe or Persistent Side Effects: Patients should seek medical advice if they experience severe or persistent side effects, such as gastrointestinal symptoms (nausea, vomiting, diarrhoea) that do not improve over time or worsen. A study reported that while gastrointestinal side effects are common with GLP-1 agonists, they typically diminish with continued use. However, severe cases can lead to dehydration and hospitalisation, necessitating medical intervention. This underscores the importance of monitoring symptoms closely.
  2. Worsening Symptoms: If existing symptoms worsen or new concerning symptoms arise—such as severe abdominal pain, changes in appetite, or significant weight losspatients should consult their doctor. Research indicates that worsening gastrointestinal symptoms can lead to complications like acute pancreatitis or gallbladder disease. A pooled analysis showed a slightly elevated risk of pancreatitis associated with GLP-1 medications, highlighting the need for vigilance in monitoring these symptoms.
  3. Concerns About Medication Safety: Patients should consult their healthcare provider if they have concerns about the safety of their medication, particularly regarding potential side effects like pancreatitis or allergic reactions.

    In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) has issued warnings about the potential risks associated with GLP-1 receptor agonists, including rare but serious side effects such as pancreatitis and severe allergic reactions. Reports indicate that some patients have experienced severe reactions requiring hospitalisation.

Conclusion

Like many treatments, GLP-1 agonists come with side effects that may impact your daily routine. While these side effects can be challenging, they often decrease over time, and many people find relief through dietary adjustments or dosage management. In your weight loss journey with GLP-1 medication, it’s essential to stay connected with your healthcare provider. Open communication is key; sharing any side effects or concerns early on helps you and your provider make timely adjustments that can improve your experience and maximise your results. By staying informed and actively involved in your treatment decisions, you are better equipped to manage the challenges and celebrate the wins that come with each step forward.

Remember, this journey is personal. Take time to weigh the benefits, understand the potential side effects, and ensure each choice aligns with your goals and comfort level. Don’t hesitate to share this article to help others make the best choices for their own journeys. 

Frequently Asked Questions

1. Are GLP-1 medications safe for long-term weight loss?

Safety depends on individual health conditions. While studies show GLP-1 medications are generally safe for weight loss, long-term use requires regular monitoring to manage any side effects and ensure sustained effectiveness. Discussing long-term plans with your healthcare provider can help you stay informed about potential risks.

2. Can GLP-1 medications affect my hormonal balance?

GLP-1 receptor agonists (Mounjaro and Wegovy) are primarily prescribed for managing type 2 diabetes and obesity by regulating blood sugar levels and appetite. However, some users have reported changes in menstrual cycles and other hormone-related symptoms during treatment. These effects may be linked to weight loss and improved insulin sensitivity, which can influence hormonal balance. For instance, studies have shown that GLP-1 receptor agonists can improve menstrual regularity in women with polycystic ovary syndrome (PCOS) by enhancing insulin sensitivity and reducing hyperandrogenism. It's important to monitor any changes and discuss them with your healthcare provider to ensure that your treatment plan remains appropriate for your overall health.

3. What should I eat while on GLP-1 medication?A balanced diet rich in lean protein, fibre, and healthy fats can help manage side effects and support weight loss. Avoiding large meals or fatty, greasy foods may also reduce symptoms like nausea. Your provider or a dietitian can offer personalised advice for maintaining an effective diet plan.

4. How long should I take GLP-1 medication for weight loss?

The duration of use depends on your health goals and how well the medication is tolerated. Some individuals may take GLP-1 medications short-term, while others may benefit from longer use under medical supervision. Regular check-ins with your provider will help determine the optimal length of treatment.

5. Can I stop GLP-1 medication if I reach my weight loss goal?

Discontinuing GLP-1 medication should be done with guidance from your healthcare provider, as stopping suddenly may cause weight regain. They may suggest a tapering approach or a maintenance plan to help sustain results.

6. How can I make an informed decision about using GLP-1 for weight loss?

Discuss your health history, weight loss goals, and potential risks with your healthcare provider. Ask questions about expected outcomes, monitoring requirements, and alternative weight loss strategies to make an informed choice that aligns with your wellness priorities.

References

  • Elsevier. (n.d.). Glucagon-like peptide-1 (GLP-1) receptor agonists. Elsevier Health. Retrieved from https://elsevier.health/en-US/preview/glucagon-like-peptide-1-glp-1-receptor-agonists
  • Drucker, D. J. (2017). Mechanisms of action and therapeutic application of glucagon-like peptide-1. Journal of Clinical Investigation, 127(10), 4032-4043. https://doi.org/10.1172/JCI93609
  • Davies, M., Pieber, T. R., Hartoft-Nielsen, M. L., Hansen, O. K., Jabbour, S., & Rosenstock, J. (2017). Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: Recommendations for clinical practice. Diabetes, Obesity and Metabolism, 19(6), 762–772. https://doi.org/10.1111/dom.12872
  • Elashoff, M., Matveyenko, A. V., Gier, B., Elashoff, R., & Butler, P. C. (2011). Pancreatitis with use of new diabetic medications: A real-world data study using the post-marketing FDA adverse event reporting system (FAERS) database. Diabetes Care, 34(6), 1234-1239. https://doi.org/10.2337/dc10-2228
  • U.S. Food and Drug Administration. (2023, October 1). FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products. Retrieved from https://www.fda.gov

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