- Type 2 diabetes mellitus, usually as the first add-on to initial treatment (NICE guidance)
- Licensed as monotherapy (except sitagliptin) or with other agents including insulin
- Fixed-dose combinations with metformin or an SGLT2 inhibitor are available
- Should not be given together with a GLP-1 receptor agonist or tirzepatide
- Reduce HbA1c by ~11mmol/mol (1%)
DPP-4 Inhibitors
DPP-4 Inhibitors
Resources
- Non-insulin diabetes medicines: a narrative review for anaesthetists and intensivists (BJA, 2025)
- Diabetes medication pharmacology (BJA Education, 2017)
- Peri-operative management of diabetes mellitus: a multidisciplinary consensus statement (Association of Anaesthetists and JBDS-IP, 2026)
- Current practice in the perioperative management of patients with diabetes mellitus: a narrative review (BJA, 2023)
- Dipeptidyl peptidase-4 (DPP-4) inhibitors, or 'gliptins', act on the incretin pathway
- Examples: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin
- They act in a glucose-dependent manner, so carry minimal risk of hypoglycaemia
- The incretin hormones GLP-1 and GIP are released from the gut in response to food
- They have several effects (see insulin physiology):
- Glucose-dependent increase in insulin secretion from β-cells
- Inhibition of glucagon secretion from α-cells
- Reduced gastric emptying
- Increased satiety
- Endogenous GLP-1 has a half-life of ~2mins as it is rapidly broken down by circulating DPP-4
- DPP-4 inhibitors prevent this breakdown, prolonging the action of endogenous incretins
- Unlike GLP-1 receptor agonists, GLP-1 is maintained at physiological concentrations
- They are therefore weight neutral and lack the marked weight loss of GLP-1 receptor agonists
Absorption
- Oral administration
Excretion
- All except linagliptin are renally excreted, requiring dose reduction in renal impairment
- Linagliptin is suitable in renal impairment without dose adjustment
Gastrointestinal
- Associated with acute pancreatitis (uncommon), highlighted by the MHRA following post-marketing reports
- Possible association with pancreatic cancer
Cardiovascular
- Possible increased risk of heart failure with saxagliptin, particularly with renal impairment, although this does not appear to be a class effect
Immunological
- Hypersensitivity reactions including anaphylaxis, angioedema and Stevens-Johnson syndrome
Nutritional and metabolic
- Minimal risk of hypoglycaemia
- Weight neutral
Perioperative management
- UK guidance advises continuing DPP-4 inhibitors irrespective of fasting duration or timing of surgery
- American, Australian and Canadian guidelines recommend withholding on the day of surgery, although they recognise continuation may be safe
- Exceptions:
- Combination products containing metformin, which may need review if eGFR <60ml/min/1.73m2 and contrast is planned
- Combination products containing an SGLT2 inhibitor
- Surgery requiring a liver reduction diet
- Low risk of hypoglycaemia; target capillary blood glucose 4-10mmol/L if not on insulin or secretagogues
- Small trials suggest DPP-4 inhibitors may be an alternative to insulin regimens peri-operatively:
- Linagliptin with correctional insulin produced slightly higher glucose than a basal-bolus regimen, but fewer hypoglycaemic events (1.6% vs. 11%)
- Sitagliptin did not reduce postoperative hyperglycaemia in CABG patients
- Restart once eating and drinking normally and any VRII has been stopped
- Review after bariatric surgery owing to rapid falls in glucose
- Prudent to withhold in critical illness given renal excretion and the small risks of pancreatitis and heart failure