GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity) and liraglutide (Victoza, Saxenda) are increasingly prescribed for type 2 diabetes and weight management in the UK. Whilst these medications offer significant therapeutic benefits, gastrointestinal side effects—including acid reflux and heartburn—are commonly reported. Understanding why GLP-1 side effects like acid reflux occur, how to manage them effectively, and when to seek medical advice is essential for anyone taking these medications. This article explores the connection between GLP-1 agonists and reflux symptoms, offering practical guidance aligned with UK clinical standards.

What Are GLP-1 Medications and How Do They Work?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily prescribed for the management of type 2 diabetes mellitus and, more recently, for weight management in adults with obesity or overweight with weight-related comorbidities. Examples available in the UK include semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide formulations.

These medications work by mimicking the action of the naturally occurring incretin hormone GLP-1, which is released from the intestine in response to food intake. The mechanism of action involves several physiological effects:

• Enhanced insulin secretion: GLP-1 agonists stimulate glucose-dependent insulin release from pancreatic beta cells, helping to lower blood glucose levels without causing hypoglycaemia when glucose levels are normal.

• Suppression of glucagon: They reduce the secretion of glucagon, a hormone that raises blood glucose, thereby further improving glycaemic control.

• Delayed gastric emptying: One of the most clinically significant effects is the slowing of gastric emptying, which prolongs the sensation of fullness and reduces postprandial glucose spikes.

• Appetite regulation: GLP-1 receptors in the brain's appetite centres reduce hunger and food intake, contributing to weight loss.

The delayed gastric emptying, whilst therapeutically beneficial for glucose control and weight management, is also responsible for many of the gastrointestinal side effects associated with these medications. GLP-1 receptor agonists rarely cause hypoglycaemia when used alone, but the risk increases when combined with insulin or sulfonylureas—your clinician may need to reduce doses of these medications.

According to NICE guidance (NG28), GLP-1 receptor agonists are recommended as treatment options for type 2 diabetes when certain criteria are met. Some agents in this class (including liraglutide, semaglutide and dulaglutide) have demonstrated cardiovascular benefits in clinical trials, though specific benefits vary by individual medication. Understanding how these medications work is essential for recognising why certain side effects, particularly those affecting the digestive system, may occur during treatment.

Can GLP-1 Agonists Cause Acid Reflux and Heartburn?

Gastrointestinal side effects are among the most commonly reported adverse reactions with GLP-1 receptor agonists, and acid reflux (gastro-oesophageal reflux) and heartburn feature prominently in patient experiences.

The delayed gastric emptying induced by GLP-1 medications means food remains in the stomach for longer periods. This prolonged gastric retention can increase intragastric pressure and potentially promote the reflux of stomach contents into the oesophagus, leading to symptoms of heartburn, regurgitation, and discomfort. Clinical trial data and post-marketing surveillance have documented gastrointestinal complaints in a substantial proportion of patients, with nausea being the most frequent (reported in 15–40% of patients depending on the specific agent and dose), followed by vomiting, diarrhoea, constipation, and dyspepsia.

Acid reflux symptoms are recognised adverse reactions in some GLP-1 product information; frequency varies by agent and dose. For example, gastro-oesophageal reflux disease (GORD) is listed as a common side effect (affecting up to 1 in 10 people) with semaglutide (Wegovy), while dyspepsia (indigestion) is common with several agents in this class. These symptoms are often most pronounced during the initial titration phase.

Many individuals prescribed these medications may have pre-existing risk factors for reflux, including obesity itself, which is a well-established independent risk factor for GORD. Pre-existing significant gastrointestinal motility disorders (such as severe gastroparesis) warrant caution with GLP-1 medications. The weight loss achieved through GLP-1 therapy may actually improve reflux symptoms in some patients over time.

The MHRA and EMA product information for GLP-1 receptor agonists list gastrointestinal disorders as very common adverse reactions. Patients should be informed that whilst these symptoms can occur, they often diminish as the body adjusts to the medication, usually within the first few weeks to months of treatment.

Managing Acid Reflux While Taking GLP-1 Drugs

If you experience acid reflux or heartburn whilst taking a GLP-1 receptor agonist, several practical management strategies can help alleviate symptoms without necessarily requiring discontinuation of your medication.

Lifestyle and dietary modifications form the cornerstone of initial management:

• Eat smaller, more frequent meals: Rather than three large meals, consider five to six smaller portions throughout the day to reduce gastric distension.

• Avoid trigger foods: Common culprits include fatty or fried foods, chocolate, caffeine, alcohol, citrus fruits, tomatoes, and spicy dishes.

• Remain upright after eating: Wait at least two to three hours after meals before lying down, and consider elevating the head of your bed by 15–20 cm.

• Eat slowly and chew thoroughly: This aids digestion and reduces the volume of food in the stomach at any one time.

• Maintain adequate hydration: Drink water between meals rather than with meals to avoid overfilling the stomach.

Pharmacological interventions may be appropriate if lifestyle measures prove insufficient. Over-the-counter antacids containing aluminium hydroxide or magnesium carbonate can provide rapid, short-term relief for occasional symptoms. For more persistent reflux, your GP may recommend:

• Proton pump inhibitors (PPIs) such as omeprazole or lansoprazole, which reduce stomach acid production and are the first-line treatment for GORD according to NICE guidance, typically for 4-8 weeks with review.

• H2-receptor antagonists like famotidine for less severe symptoms.

• Alginates (e.g., Gaviscon) which form a protective barrier on top of stomach contents.

It is important to discuss any new symptoms with your prescribing clinician before starting additional medications, as they can assess whether dose adjustment of your GLP-1 agonist might be beneficial. Some patients find that holding at the current GLP-1 dose longer or stepping back one dose until symptoms settle can be helpful. Your healthcare team can also evaluate whether the benefits of continuing GLP-1 therapy outweigh the discomfort, or whether alternative diabetes or weight management strategies should be considered.

When to Seek Medical Advice About GLP-1 Side Effects

Whilst mild gastrointestinal symptoms are common and often transient with GLP-1 receptor agonists, certain warning signs warrant prompt medical attention. Understanding when to contact your GP or seek urgent care is essential for patient safety.

Contact your GP or diabetes specialist nurse if you experience:

• Persistent or worsening reflux symptoms that do not improve with lifestyle modifications or over-the-counter remedies after two weeks.

• Difficulty swallowing (dysphagia) or pain when swallowing, which may indicate oesophageal complications and requires urgent assessment at any age.

• Unintentional weight loss beyond what is expected from the medication, or inability to maintain adequate nutrition due to gastrointestinal symptoms.

• Persistent nausea and vomiting that prevents you from keeping down food, fluids, or other essential medications.

• Signs of dehydration: reduced urination, dark urine, dizziness, dry mouth, or confusion.

• If you are aged 55 or over with weight loss and upper abdominal pain, reflux or dyspepsia, as these may require urgent referral under NICE suspected cancer guidelines.

Seek urgent medical attention (call 111, contact your GP urgently, or attend A&E) if you develop:

• Severe, persistent abdominal pain, particularly if it radiates to the back, as this may indicate pancreatitis—a rare but serious adverse effect of GLP-1 agonists. Stop your GLP-1 medicine immediately if pancreatitis is suspected; do not restart if pancreatitis is confirmed.

• Right upper abdominal pain, fever or jaundice, which could indicate gallbladder disease, another potential complication.

• Vomiting blood or passing black, tarry stools, which could suggest gastrointestinal bleeding.

• Severe chest pain that differs from typical heartburn, especially if accompanied by shortness of breath—call 999 if you suspect a cardiac cause.

• Severe bloating, persistent vomiting, or failure to pass stool or gas, which may indicate bowel obstruction or severe gastroparesis.

• Signs of severe allergic reaction: facial swelling, difficulty breathing, or widespread rash.

According to NICE guidance and MHRA safety information, healthcare professionals should maintain vigilance for rare but serious adverse effects including acute pancreatitis, gallbladder disease, and potential thyroid tumours (based on animal studies, though human risk remains uncertain). Regular monitoring and open communication with your healthcare team ensure that any concerning symptoms are evaluated promptly.

Never discontinue prescribed medication without consulting your doctor, as abrupt cessation may affect your diabetes control or weight management goals. If you suspect you have experienced a side effect from a GLP-1 medication, you can report it through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions