- Type 2 diabetes mellitus (NICE guidance)
- Subcutaneous semaglutide is offered to those with atherosclerotic cardiovascular disease
- A GLP-1 RA or tirzepatide is considered in obesity or early-onset T2DM
- Should not be combined with a DPP-4 inhibitor
- Reduce rates of non-fatal myocardial infarction, stroke and cardiovascular death in patients with T2DM at high cardiovascular risk (e.g. the LEADER and SUSTAIN-6 trials)
- Weight management in people without diabetes (liraglutide, semaglutide, tirzepatide)
- Mean weight loss of ~15%, which was previously only seen with bariatric surgery
- Reduce HbA1c by ~11mmol/mol (1%)
GLP-1 Receptor Agonists
GLP-1 Receptor Agonists
Resources
- Glucagon-like peptide-1 receptor agonists: a narrative review of clinical pharmacology and implications for peri-operative practice (Anaesthesia, 2024)
- Non-insulin diabetes medicines: a narrative review for anaesthetists and intensivists (BJA, 2025)
- Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US FDA adverse event reporting system (BJA, 2025)
- Peri-operative management of diabetes mellitus: a multidisciplinary consensus statement (Association of Anaesthetists and JBDS-IP, 2026)
- Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists and sodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement (Anaesthesia, 2025)
- Update on the perioperative management of diabetes mellitus (BJA Education, 2024)
- Diabetes medication pharmacology (BJA Education, 2017)
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) mimic the incretin hormone GLP-1
- They are used increasingly for type 2 diabetes and, more recently, for weight management in people without diabetes
- Their key peri-operative concern is delayed gastric emptying and the risk of pulmonary aspiration
- Drugs in this class typically end in '-natide' or '-glutide' although tirzepatide is a dual GIP/GLP-1 receptor agonist
| Drug | Trade name | Half-life | Typical dosing | Three half-lives |
| Exenatide | Byetta | 2.4hrs | 5-10μg SC twice daily | ~7hrs |
| Liraglutide | Victoza, Saxenda | 13hrs | 0.6-1.8mg SC daily (3mg for weight loss) | ~39hrs |
| Dulaglutide | Trulicity | ~4 days | 0.75-1.5mg SC weekly | ~11 days |
| Semaglutide (SC) | Ozempic, Wegovy | ~7 days | 0.25-1mg SC weekly (2.4mg for weight loss) | ~3 weeks |
| Semaglutide (oral) | Rybelsus | ~7 days | 3-14mg orally daily | ~3 weeks |
| Tirzepatide | Mounjaro | ~5 days | 2.5-15mg SC weekly | ~15 days |
- All are modified to resist DPP-4 cleavage, which gives endogenous GLP-1 its 2min half-life
- Long-acting agents are modified further e.g. albumin binding (semaglutide) or Fc-fragment conjugation (dulaglutide)
- Peptides, so most require subcutaneous injection
- Doses are titrated up slowly to improve GI tolerability
- GLP-1 is released from intestinal L-cells in response to glucose and triglycerides
- GLP-1 RAs activate the G-protein coupled GLP-1 receptor
- β-cells: ↑ intracellular Ca2+ causes glucose-dependent insulin exocytosis, so the risk of hypoglycaemia is very low
- α-cells: glucagon secretion is inhibited, mediated by somatostatin from adjacent δ-cells
- Hypothalamus and brainstem: ↓ appetite and ↑ satiety
- Much of their glucose-lowering effect comes from delayed gastric emptying rather than their effect on the islets
Delayed gastric emptying
- Mediated via the vagus nerve; the effect is absent after vagotomy
- Receptors on the myenteric plexus inhibit vagal activity on the gut, causing:
- Reduced gastric peristalsis and increased pyloric tone
- Reduced gastric acid secretion
- Increased fasting and postprandial gastric volumes
- Most marked in the first postprandial hours
- Whether tachyphylaxis develops is debated:
- Some data suggest gastric emptying normalises after ~12 weeks of continuous treatment
- However, a meta-analysis of scintigraphy studies found no significant attenuation over time
Cardiovascular
- Cardioprotective: anti-inflammatory and anti-atherosclerotic effects, improved myocardial substrate use
- ↓ systolic blood pressure
- ↑ heart rate, as receptors are found at the sinoatrial node (can cause tachyarrhythmias in rare cases)
Neurological
- ↓ appetite and energy intake via the arcuate nucleus, nucleus tractus solitarius and area postrema
Gastrointestinal
- Delayed gastric motility and emptying; ↓ gastric secretions
- Consequent higher risk of aspiration and regurgitation under anaesthesia despite adequate fasting times
- Hepatic: ↓ glucose production, ↑ glucose uptake
- GI side-effects
- Nausea, vomiting and diarrhoea (dose-dependent and more frequent with short-acting agents)
- Dyspepsia, reflux and constipation
- Gallbladder disease
- Acute pancreatitis (rare) although use with caution if previous pancreatitis
Endocrine
- ↑ glucose-dependent insulin release and synthesis
- ↓ postprandial glucagon secretion
- May promote β-cell proliferation and reduce apoptosis
MSK
- ↑ skeletal muscle glucose uptake
Perioperative management
Risk assessment
- Document the indication and dose, when the drug was started, any recent dose changes and the last dose
- Features that increase the risk of retained gastric contents:
- Recent initiation or dose escalation, or high doses
- GI symptoms: nausea, vomiting, abdominal distension
- Diabetes with poor glycaemic control or autonomic neuropathy
- Previous gastro-oesophageal surgery, reflux, obesity
- Co-prescribed drugs that delay gastric emptying (opioids, tricyclic antidepressants) or recent alcohol or cannabis use
UK guidance
- UK multidisciplinary consensus (Association of Anaesthetists, 2025) and CPOC recommend continuing GLP-1 RAs with an individual risk assessment and shared decision-making
- Higher-risk patients may be managed by altering the anaesthetic technique or the fasting regimen, e.g. a 24hr clear fluid diet before the procedure
- Consider postponing elective surgery in patients with GI symptoms on the day
International approaches
- The ASA initially (2023) recommended withholding daily agents on the day of surgery and weekly agents for a week although this was reversed in 2024 in favour of risk assessment
- Some guidance suggest withholding for at least three half-lives (~88% clearance) when used for weight loss, with endocrinology input if used for diabetes
- There is, however, no strong evidence that gastric emptying normalises after this time
Risks of stopping
- Worsening glycaemic control in patients with diabetes
- Omitting more than two doses means reintroduction must restart at the lowest dose, prolonging glycaemic variability
- Point-of-care gastric ultrasound can guide decision-making where available
- Consider avoiding GA, rapid sequence induction or prokinetics in higher-risk patients
- Pre-emptive gastric decompression with a nasogastric tube may be considered in very high-risk patients, although it does not remove solids effectively
- Restart once eating and drinking
- Prudent to withhold in critical illness given their GI effects, unpredictable subcutaneous absorption and associations with pancreatitis and acute kidney injury
- Their long half-lives mean effects persist for some time after discontinuation