MHRA Drug Safety Update: GLP-1 agonists and pulmonary aspiration

In a Drug Safety Update issued in January 2025, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) warned that GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists may increase the risk of pulmonary aspiration during general anaesthesia or deep sedation.

The affected medicines include semaglutide (Ozempic, Rybelsus, Wegovy), tirzepatide (Mounjaro), liraglutide (Saxenda, Victoza), dulaglutide (Trulicity), and lixisenatide (Lyxumia).

Mechanism: delayed gastric emptying

GLP-1 receptor agonists slow gastric emptying — a known pharmacological effect that contributes to their appetite-suppressing and glycaemic benefits. However, this delayed emptying means that food and gastric contents may remain in the stomach for longer than expected, increasing the risk of regurgitation and pulmonary aspiration during procedures requiring general anaesthesia or deep sedation.

Dual GIP/GLP-1 receptor agonists such as tirzepatide carry the same risk profile.

MHRA recommendations

The MHRA advises healthcare professionals to:

  • Be aware that patients taking GLP-1 receptor agonists or dual GIP/GLP-1 agonists may be at increased risk of pulmonary aspiration during general anaesthesia or deep sedation.
  • Consider whether withholding these medicines before a procedure is appropriate, taking into account the pharmacokinetic properties of the specific medicine (half-life varies considerably between products).
  • Follow existing fasting guidance for procedures, while recognising that standard fasting periods may be insufficient for patients on GLP-1 agonists due to delayed gastric emptying.
  • Report suspected adverse reactions via the Yellow Card scheme.

The guidance does not constitute a contraindication but represents a precautionary safety signal aimed at anaesthetists, surgeons, and prescribers involved in perioperative care.

Context for peptide researchers

This safety signal is relevant to the broader peptide research community for several reasons:

  • It reinforces that delayed gastric emptying is a clinically significant pharmacological effect of GLP-1 agonism, not merely a tolerability issue.
  • It highlights the importance of understanding the pharmacokinetic profile — particularly half-life — of any GLP-1-active peptide, as this determines how long the delayed-emptying effect persists after dosing.
  • For research involving GLP-1, dual GIP/GLP-1, or triple-agonist peptides (such as retatrutide), this safety signal is relevant context for understanding the real-world clinical risk profile of this drug class.

Related peptides

This guidance applies to all GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, including those covered in our compound profiles: semaglutide, tirzepatide, liraglutide, lixisenatide, and exenatide. Emerging dual and triple agonists such as retatrutide and survodutide are expected to carry similar risks due to their GLP-1 agonist component.

UK regulatory status

GLP-1 receptor agonists are Prescription-Only Medicines (POM) in the UK. Semaglutide (Wegovy) and tirzepatide (Mounjaro) are licensed for weight management; semaglutide (Ozempic), tirzepatide (Mounjaro), liraglutide (Victoza), dulaglutide, and lixisenatide are licensed for type 2 diabetes. Research-grade peptides are not licensed medicines and must not be presented as alternatives to regulated pharmaceutical products.

This article is for research and educational purposes only and does not constitute medical advice.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.