GLP-1 receptor agonists, the class that includes semaglutide and tirzepatide, work in large part through the digestive tract. They slow gastric emptying, reduce appetite and change how quickly food moves through the stomach. That mechanism is the reason they are effective, and also the reason almost every common side effect is gastrointestinal.
Most of those side effects are manageable. One consideration is not a side effect at all, but a safety issue that arises only when a patient on these drugs undergoes an endoscopy or any procedure under sedation. It is the single most important thing a patient on a GLP-1 needs to know before booking a gastroscopy or colonoscopy.
The common side effects
Frequencies come from the European Medicines Agency product information for each medicine, and they differ substantially depending on the dose and the indication.
For semaglutide at weight management doses, compared with placebo:
- Nausea: 43.9% versus 16.1%
- Diarrhoea: 29.7% versus 15.9%
- Vomiting: 24.5% versus 6.3%
- Constipation: 24.2% versus 11.1%
At the lower doses used for type 2 diabetes, the figures are considerably lower, with nausea around 17% to 20% and diarrhoea around 12% to 13%.
For tirzepatide, nausea, diarrhoea, vomiting, abdominal pain and constipation are all classed as very common. In pooled analysis, 74% of gastrointestinal reactions were mild and 23.3% moderate.
Two patterns are worth knowing:
Timing. Symptoms cluster around starting the drug and around each dose increase, and they settle once a maintenance dose is reached. Median durations reported for semaglutide were eight days for nausea, two days for vomiting and three days for diarrhoea.
The exception is constipation, with a reported median duration of 47 days. It is the symptom most likely to persist and the one most often left untreated because patients assume it will pass like the others.
Delayed gastric emptying
Slowed gastric emptying is an expected pharmacological effect, not a complication. With the long-acting agents, the effect attenuates over weeks as the body adapts, a phenomenon called tachyphylaxis. One meta-analysis found gastric emptying delayed by around 36 minutes compared with placebo at four hours, which is not clinically significant within normal daily life.
The effect is not uniform. Some patients have a marked delay, others very little, and those with naturally slower emptying show less drug effect.
Gastroparesis, pancreatitis and gallstones: what the evidence actually shows
These three are the associations patients read about online, and they deserve honest separation.
Gallbladder disease is the best established. A meta-analysis of randomised trials found a 37% increase in biliary and gallbladder disease overall, with the risk more than doubled at weight loss doses compared with a 27% increase at diabetes doses, and rising with higher dose and longer duration. An important caveat: rapid weight loss by any means causes gallstones, so how much of this belongs to the drug rather than to the weight loss is contested.
Pancreatitis is labelled but not supported by trial data. In the LEADER trial pancreatitis occurred in 0.4% on liraglutide versus 0.5% on placebo. A network meta-analysis of over 100,000 participants found a relative risk of 0.96. Regulatory labelling classes acute pancreatitis as rare or uncommon. The widely cited 2023 study reporting a ninefold increase had very wide confidence intervals and was explicitly hypothesis generating.
True gastroparesis appears to be rare and reversible. A systematic review covering the literature through October 2025 found only 12 case reports, 13 patients in total, of symptomatic GLP-1 associated gastroparesis. Onset ranged from hours to months after starting, was associated with rapid dose escalation, and symptoms resolved in all cases after the drug was stopped. Figures circulating online claiming that 1% to 3% of users develop gastroparesis are not supported by any published study.
Before an endoscopy: the part that matters
The concern is simple. If the stomach empties more slowly, food may still be present at the time of sedation, even after a standard fasting period. Retained stomach contents can force the procedure to be abandoned or, rarely, be aspirated into the lungs.
The evidence separates those two risks clearly.
Retained gastric contents are definitely increased. A meta-analysis of 13 studies covering more than 84,000 patients found roughly a fivefold increase in retained stomach contents in GLP-1 users. In absolute terms, around 9% of GLP-1 users had retained contents at upper endoscopy, rising to nearly 12% in those with symptoms.
Clinical aspiration is not clearly increased. In that same meta-analysis, aspiration occurred in 0.3% of GLP-1 users versus 0.2% of non-users, a difference that was not statistically significant. A larger analysis of over 212,000 individuals found the same. Pooled data across surgery and endoscopy found no elevated aspiration risk.
The 2026 randomised trial. The OCULUS trial, published in March 2026, randomised patients to hold or continue their GLP-1 before endoscopy. Clinically significant residual gastric volume occurred in 3.1% of those who held the drug versus 25.0% of those who continued. There were no aspiration events, intubations or hospitalisations in either group. Most importantly, among patients who had a same-day colonoscopy and therefore drank only clear liquids the day before, there were no cases of clinically significant residual volume in either group.
What the guidance says now
The picture has changed significantly since 2023, when anaesthesia guidance recommended holding weekly GLP-1 doses for a full week before any procedure.
No major society now recommends universal withholding. The current position, across multi-society guidance from the United States, the United Kingdom and Australia and New Zealand, converges on four points:
- Do not routinely stop the medication before a procedure
- A clear liquid diet on the day before is the main practical mitigation
- Assess risk individually, taking into account the dose escalation phase, high doses, weekly agents, gastrointestinal symptoms, diabetic gastroparesis and reflux
- Treat the decision as a shared one between endoscopist, anaesthetist and prescribing doctor
The European Society of Gastrointestinal Endoscopy, in its sedation guideline published in July 2026, suggests that sedation management in patients on GLP-1 receptor agonists should be individualised, a conditional recommendation based on very low certainty evidence.
The European Medicines Agency required a warning in the product information of all these medicines in 2024, noting that the increased risk of residual gastric content should be considered before procedures involving general anaesthesia or deep sedation.
One further point applies specifically to colonoscopy. A meta-analysis of five studies found inadequate bowel preparation was roughly twice as common in GLP-1 users, at 10.6% versus 4.6%. There is no formal society recommendation on how to intensify preparation for these patients, so it is a matter for individual judgement.
What to do as a patient
- Tell your doctor and your anaesthetist that you take a GLP-1, before any procedure involving sedation or anaesthesia. This applies to weight loss prescriptions as much as to diabetes ones. Clinicians are now advised to ask directly, because patients often do not think to mention them.
- Do not stop a diabetes medication on your own. Whether to hold a dose is a decision for the team managing your procedure together with the doctor who prescribed it.
- Expect different fasting instructions. A clear liquid diet the day before is common practice and is the measure with the best supporting evidence.
- Report symptoms before the procedure. Nausea, vomiting, bloating or a feeling of fullness are relevant. Be aware, though, that the absence of symptoms does not guarantee an empty stomach.
- Titrate slowly. Gastrointestinal effects concentrate in the dose escalation phase, and the reported cases of severe delayed emptying were linked to rapid escalation.
When to see a doctor
Contact your doctor if, while taking a GLP-1, you experience:
- Persistent vomiting, or inability to keep fluids down
- Severe abdominal pain, particularly if it radiates to the back, which needs urgent assessment
- Constipation that does not respond to simple measures
- Symptoms suggesting gallstones: pain in the right upper abdomen after meals, fever, or yellowing of the skin or eyes
- Bloating and fullness severe enough to interfere with eating
Most gastrointestinal effects of these medicines are transient and dose related. The ones that need attention are those that persist, worsen, or prevent you from eating and drinking normally.