GLP what?!

There is a lot of hype about these drugs. From celebs, to every day weight loss seekers. But, it all came off the back of their usage for their primary indication; sugar control. As many as 1 in 20 of our patients could be taking these drugs!

Names in the game!

• Exenatide (Byetta, Bydureon)
• Liraglutide (Victoza, Saxenda)
• Dulaglutide (Trulicity)
• Semaglutide (Ozempic, Wegovy, Rybelsus)
• Tirzepatide (Mounjaro)

The above 5 account for 49.5% (982 of 1982) of the reports of cases where delayed gastric emptying (DGE) was significant.

But, the DGE effects are very delayed! The peak of the effect is early on during treatment initiation. Peak DGE effects:

• Semaglutide: 40.5 days
• Liraglutide: 42 days
• Dulaglutide: 44 days
• Exenatide: 60 days
• Tirzepatide: 107.5 days

Risks of DGE are lower in the elderly, the higher the BMI and in males.

How GLP-1 Drugs Work and Their Popularity for Weight Loss

GLP-1 receptor agonists, such as semaglutide (Ozempic®, Wegovy®), and dual GLP-1/GIP receptor agonists, like tirzepatide (Mounjaro®), are game-changers in managing type 2 diabetes and obesity. But how do they work, and why have they become so popular for weight loss?

These drugs mimic natural hormones in the body. Semaglutide acts like glucagon-like peptide-1 (GLP-1), a hormone that helps control blood sugar by boosting insulin release after meals. It also slows down how quickly food moves through the stomach, making you feel full for longer.

Tirzepatide goes a step further, mimicking both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), another hormone that enhances insulin production and fat metabolism. This dual action makes tirzepatide especially powerful.

For weight loss, these drugs shine because they:

• Reduce Appetite: They signal the brain to feel satisfied, so patients eat less without feeling deprived.
• Slow Digestion: Food stays in the stomach longer, curbing hunger between meals.
  • Some studies report solid food remnants in the stomach even after prolonged fasting.
  • However, no direct link has been found between GLP-1R agonists and higher pulmonary aspiration risk.
• Improve Metabolism: They help the body use energy more efficiently, especially with tirzepatide’s GIP effect.
  • There’s a lower risk of hypoglycaemia than insulin and better perioperative glucose control.
  • Stopping GLP-1R agonists preoperatively may lead to worsened glycaemia and metabolic instability.

Their popularity stems from impressive results. Clinical trials show semaglutide (Wegovy®) can help patients lose 15–20% of their body weight, while tirzepatide (Mounjaro®) may lead to even greater losses, up to 20–25%. Unlike older weight loss drugs, these injectables are highly effective, with manageable side effects like nausea that often improve over time. Their once-weekly dosing (or daily for some formulations) is convenient, and their success in high-profile cases has fueled public demand, especially for off-label use in non-diabetic patients seeking weight loss.

However, this delayed gastric emptying, while great for weight loss, poses an often hidden anaesthesia risk!

A fantastic podcast about it all here

Navigating the Perioperative Challenges of GLP-1 Receptor Agonists: Aspiration Risks and Anaesthetic Considerations

Coming across patients taking one of these drugs is becoming common place. But, watch it! Sometimes patients withhold the fact they are on the drug, considering it a harmless ‘cosmetic’ adjunct. This withholding of such information, I am sure is not calculated, nor deliberate in most cases. But, a drug you jabbed into your abdomen a good few days ago is perfectly benign right?!

Wrong!

The risk of pulmonary aspiration during general anaesthesia or deep sedation is real. Starvation protocols are meaningless. We will explore the advice out there on these drugs, as information is new, nuanced and not well known!

The Aspiration Risk: Why GLP-1 RAs Matter in Anaesthesia

Because of their effect upon gastric emptying, one has to consider a patient who has recently taken one of these drugs as having a full stomach. Therefore the risk of regurgitation and pulmonary aspiration sits high on your list.

Case reports have highlighted this concern: for instance, a patient on semaglutide for weight loss experienced pulmonary aspiration during an elective procedure despite fasting for 18 hours, requiring ICU admission. Another study found that patients taking semaglutide were five times more likely to have increased RGC during upper endoscopy, even after adhering to fasting guidelines.

The Medicines and Healthcare products Regulatory Agency (MHRA) has reported rare cases of aspiration linked to GLP-1 RAs, including one instance of aspiration pneumonia as of December 2024. These incidents underscore the need for anaesthetists to identify patients on these medications early, ideally at the preoperative assessment stage, and tailor their management to mitigate risks.

Understanding the Drugs and Their Pharmacokinetics

Semaglutide, available as Ozempic® (for T2DM), Wegovy® (for weight loss), and Rybelsus® (oral formulation), and tirzepatide (Mounjaro®, a dual GLP-1/GIP receptor agonist), are long-acting agents with significant half-lives.

• Semaglutide has a half-life of approximately 7 days, meaning it takes about 3–4 weeks (3–4 half-lives) for 88–94% of the drug to be cleared from the system.
• Tirzepatide’s half-life is around 5 days, requiring roughly 2–3 weeks for similar clearance. This prolonged presence complicates perioperative planning, as the delayed gastric emptying effect may persist well beyond the last dose.

Guidance from the Association of Anaesthetists and Royal College of Anaesthetists

In January 2025, the Association of Anaesthetists, in collaboration with the Royal College of Anaesthetists and other professional bodies, published a multidisciplinary consensus statement on the elective perioperative management of adults taking GLP-1 RAs. This guidance, endorsed by Toni Brunning, Vice President of the RCoA, advises a balanced approach to mitigate aspiration risk while maintaining the benefits of these medications, particularly for diabetic patients. Key recommendations include:

1. Continue GLP-1 RAs as Normal for Most Patients: Unlike earlier suggestions to withhold these drugs, the consensus recommends that patients continue GLP-1 RAs (daily or weekly dosing) up to the day of surgery, provided a thorough risk assessment is conducted. This shift reflects concerns about the adverse effects of cessation, such as hyperglycaemia in diabetic patients, which could complicate perioperative outcomes.
2. Individualised Risk Assessment: Anaesthetists should assess patients for factors that increase aspiration risk, including:
   • Gastrointestinal Symptoms: Nausea, vomiting, abdominal bloating, or constipation suggest delayed gastric emptying.
   • Dose Escalation Phase: Patients in the first 4–8 weeks of treatment, when doses are titrated, are at higher risk of gastrointestinal side effects.
   • Comorbidities: Conditions like diabetic gastroparesis, obesity, or gastroesophageal reflux disease exacerbate the risk.
   • Higher Doses: Weight loss doses (e.g., Wegovy 2.4 mg vs. Ozempic 1 mg) are associated with more pronounced effect on gastric emptying.
3. Perioperative Mitigation Strategies:
   • Liquid Diet: For high-risk patients (e.g., those with GI symptoms or in the dose escalation phase), a 24-hour liquid-only diet before surgery can reduce gastric contents.
   • Point-of-Care Gastric Ultrasound: Where available, ultrasound can assess RGC immediately before anaesthesia, though its use is limited by institutional resources and operator expertise.
   • Anaesthetic Technique Adjustments: Rapid sequence induction or full-stomach precautions (e.g., endotracheal intubation) may be necessary for high-risk cases, especially in procedures requiring deep sedation where the airway is unprotected.
   • Prokinetic Drugs: Some suggest using agents like metoclopramide to enhance gastric emptying, though evidence is limited.
4. Delay Elective Procedures if Necessary: Surgery should be postponed for patients with significant GI symptoms or those in the dose escalation phase until symptoms resolve or the escalation period ends.
5. Patient Communication: Patients must inform their healthcare team, including anaesthetists, about GLP-1 RA use, as privately purchased medications may not appear in medical records.
6. After the op
   • Restart GLP-1R agonists by gradually titrating to avoid severe gastrointestinal symptoms.
   • Patients may experience dehydration and malnutrition due to prolonged nausea and reduced appetite.

Contrasting with Earlier Guidance

The 2025 AAGBI/RCoA guidance contrasts with earlier recommendations from the American Society of Anesthesiologists (ASA), which in 2023 advised withholding daily GLP-1 RAs on the day of surgery and weekly formulations (e.g., semaglutide) one week prior. Some experts argued for even longer cessation—up to three half-lives (e.g., 3 weeks for semaglutide)—to ensure minimal drug activity. However, the AAGBI/RCoA consensus prioritises continuing therapy to avoid disrupting glycaemic control, especially given the lack of high-quality prospective studies confirming a significant aspiration risk in the perioperative setting. This approach aligns with shared decision-making, balancing aspiration risk against the metabolic consequences of stopping the drug.

Practical Recommendations for Anaesthetists

To ensure patient safety, anaesthetists should:

• Screen Early: Include GLP-1 RA use in preoperative questionnaires, as patients may not volunteer this information.
• Assess Risk Factors: Evaluate GI symptoms, dose escalation, and comorbidities at the pre-assessment clinic.
• Consult Endocrinologists: For diabetic patients, coordinate with endocrinologists to manage glycaemic control if prolonged cessation is considered.
• Educate Patients: Reinforce the importance of disclosing GLP-1 RA use and adhering to tailored fasting or diet instructions.
• Stay Updated: Monitor emerging research, as the evidence base for GLP-1 RAs in anaesthesia is evolving rapidly.

Conclusion

GLP-1 receptor agonists like semaglutide and tirzepatide present both opportunities and challenges in the perioperative setting. Their delayed gastric emptying effect heightens aspiration risk, necessitating careful preoperative planning. The 2025 AAGBI and RCoA consensus statement advocates continuing these medications for most patients, coupled with individualised risk assessments and mitigation strategies like liquid diets or gastric ultrasound. By integrating these guidelines into practice, anaesthetists can safely manage patients on GLP-1 RAs, ensuring optimal outcomes while addressing the complexities of modern pharmacotherapy.

• GLP-1 receptor agonists are strongly associated with DGE.
• The risk is highest early in therapy, with significant implications for surgical safety.
• Age, weight, and sex are meaningful modifiers of DGE risk.
• Pulmonary aspiration, though rare, can be life-threatening.
• Personalized perioperative planning is essential for patients on GLP-1RAs.

My take…history and more history before you anaesthetise! Don’t get caught short…oh, and learn simple POCUS gastric ultrasound!

JW