Ozempic (semaglutide) is a GLP-1 receptor agonist licensed in the UK for type 2 diabetes management, but concerns have emerged about whether it increases gallstone risk. Whilst Ozempic itself does not directly cause gallstones, the rapid weight loss it facilitates can alter bile composition and gallbladder function, creating conditions that favour gallstone formation. Clinical evidence suggests a small increased risk of gallbladder-related complications during semaglutide therapy. Understanding this association, recognising warning symptoms, and implementing preventive strategies can help patients and clinicians manage this potential complication whilst benefiting from improved glycaemic control and weight reduction.

What Is Ozempic and How Does It Work?

Ozempic (semaglutide) is a prescription medication licensed in the UK for the treatment of type 2 diabetes mellitus. It belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists, which mimic the action of a naturally occurring hormone that regulates blood sugar levels and appetite.

The mechanism of action involves several key processes:

• Enhancing insulin secretion from the pancreas in response to elevated blood glucose

• Suppressing glucagon release, which reduces glucose production by the liver

• Slowing gastric emptying, which prolongs the feeling of fullness after meals

• Acting on appetite centres in the brain to reduce hunger and food intake

Ozempic is administered as a once-weekly subcutaneous injection. Treatment typically starts with 0.25 mg for 4 weeks as an initiation dose (not intended for glycaemic control), then increases to maintenance doses of 0.5 mg, 1 mg, or 2 mg, depending on individual response and tolerability. The MHRA has approved it specifically for glycaemic control in adults with type 2 diabetes, often in combination with other glucose-lowering medications or as monotherapy when metformin is unsuitable.

A secondary benefit of semaglutide therapy is weight loss, with clinical trials showing average reductions of approximately 3-6 kg (or 3-6% of body weight) over 30-56 weeks in people with type 2 diabetes. The SUSTAIN-6 trial also demonstrated a reduction in major adverse cardiovascular events in patients with type 2 diabetes at high cardiovascular risk, though this is not a specific licensed indication in the UK.

It's important to note that Ozempic is distinct from Wegovy, which is the same molecule (semaglutide) but licensed specifically for weight management at higher doses.

Why Rapid Weight Loss Can Increase Gallstone Risk

Gallstones (cholelithiasis) are solid deposits that form in the gallbladder, typically composed of cholesterol or bilirubin. The relationship between Ozempic and gallstones appears to be primarily mediated through weight loss, though GLP-1 receptor agonists may also directly affect gallbladder emptying and motility.

When the body loses weight quickly, several metabolic changes occur that predispose to gallstone development:

• Increased cholesterol secretion into bile as the body mobilises fat stores

• Reduced gallbladder motility and emptying, leading to bile stasis

• Altered bile composition, with a higher ratio of cholesterol to bile salts

• Decreased gallbladder contractility, partly due to reduced food intake and prolonged fasting periods

Very rapid weight loss, such as that following bariatric surgery, has been associated with gallstone formation in approximately 10-25% of patients. While the risk with GLP-1 receptor agonists appears lower, clinical trials and post-marketing surveillance of semaglutide have identified a small increased risk of gallbladder-related adverse events, including cholelithiasis and cholecystitis (gallbladder inflammation), compared to placebo.

It is important to note that obesity itself is an independent risk factor for gallstones, so patients starting Ozempic may already have elevated baseline risk. Other contributing factors include female sex, age over 40, rapid weight cycling, and certain ethnic backgrounds. The UK SmPC for Ozempic notes the potential for gallbladder disorders during treatment, particularly in the context of substantial weight loss.

Symptoms of Gallstones to Watch For

Many people with gallstones remain asymptomatic and may never require treatment. However, when gallstones obstruct the bile ducts or cause inflammation, they can produce characteristic symptoms that warrant medical attention. Patients taking Ozempic should be vigilant for the following signs:

Biliary colic is the hallmark symptom, characterised by:

• Sudden, severe pain in the right upper quadrant or epigastrium

• Pain that may radiate to the right shoulder or back (particularly between the shoulder blades)

• Episodes typically lasting 30 minutes to several hours

• Pain often triggered by fatty meals, though it can occur spontaneously

• Associated nausea and vomiting

Acute cholecystitis (gallbladder inflammation) presents with more persistent symptoms:

• Continuous right upper quadrant pain lasting more than 6 hours

• Fever and rigors indicating infection

• Tenderness on examination (Murphy's sign)

• Jaundice (yellowing of skin and eyes), dark urine, and pale stools if bile duct obstruction occurs

More serious complications, though less common, include ascending cholangitis (bile duct infection) and pancreatitis (inflammation of the pancreas), both of which constitute medical emergencies.

When to seek medical attention:

• Contact your GP promptly if you experience recurrent episodes of right upper abdominal pain

• Seek urgent medical assessment (A&E or call 999) if you develop severe persistent pain, high fever, jaundice, or signs of sepsis

• If you develop severe, persistent abdominal pain that radiates to your back, especially with vomiting, seek urgent medical care as this could indicate pancreatitis. If pancreatitis is suspected, semaglutide should be stopped and not restarted if pancreatitis is confirmed

• Inform healthcare professionals that you are taking Ozempic and have experienced significant weight loss

Early recognition and appropriate investigation—typically including blood tests (full blood count, liver function tests, CRP, amylase/lipase) and ultrasound imaging—can prevent serious complications and guide timely management decisions.

Reducing Your Risk While Taking Ozempic

Whilst the gallstone risk associated with rapid weight loss cannot be entirely eliminated, several evidence-based strategies can help minimise this complication during Ozempic therapy:

Gradual dose escalation and weight loss:

• Follow the prescribed titration schedule carefully, allowing your body to adjust

• Aim for steady, moderate weight loss rather than rapid reduction

• Work with your healthcare team to set realistic weight loss targets

Dietary modifications:

• Maintain regular meal patterns rather than prolonged fasting, which promotes gallbladder emptying

• Include moderate amounts of healthy fats in your diet (such as olive oil, nuts, and oily fish) to stimulate gallbladder contraction

• Avoid very low-fat or crash diets, which paradoxically increase gallstone risk

• Ensure adequate fibre intake and hydration

Medical monitoring:

• Attend regular follow-up appointments to monitor weight loss trajectory and overall response

• Report any new abdominal symptoms promptly to your GP or diabetes specialist

• If you have pre-existing gallstones (known from previous imaging), discuss this with your prescriber before starting Ozempic

• Contact your prescriber if you develop symptoms suggestive of gallbladder problems; they may advise temporarily pausing semaglutide pending clinical assessment

NICE guidance on diabetes management (NG28) and gallstone disease (CG188) emphasises the importance of multidisciplinary support, including dietetic input, which can help optimise nutritional intake whilst achieving therapeutic weight loss.

It is crucial to remember that the benefits of Ozempic therapy—including improved glycaemic control and weight reduction—generally outweigh the relatively small risk of gallstone formation for most patients. However, informed patients who understand the warning signs and maintain appropriate medical follow-up can safely navigate this potential complication.

If you suspect you're experiencing side effects from Ozempic, report them to the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk) and discuss any concerns with your healthcare provider rather than discontinuing medication independently.

Frequently Asked Questions