Synopsis
Choose incretin-based treatment safely, distinguish DPP-4 from GLP-1 and dual GIP–GLP-1 therapy, and monitor benefit, pregnancy, pancreatitis and perioperative risk.
- DPP-4 inhibitors prolong endogenous incretin action, are weight neutral and have low hypoglycaemia risk alone; their glucose-lowering effect is modest compared with injectable GLP-1 or tirzepatide.
- GLP-1 receptor agonists increase glucose-dependent insulin, suppress glucagon, slow gastric emptying and promote satiety; tirzepatide activates both GIP and GLP-1 receptors.
- Use the February 2026 NICE NG28 phenotype-based algorithm and licensed indication; diabetes and weight-management brands, doses and eligibility are not interchangeable.
- Do not combine a DPP-4 inhibitor with a GLP-1 receptor agonist or tirzepatide because overlapping incretin mechanisms add burden without recommended benefit.
- Titrate GLP-1 or tirzepatide slowly through the product schedule and review nausea, intake, hydration, weight trajectory and renal function rather than escalating automatically.
- MHRA strengthened the whole-class pancreatitis warning in January 2026, including rare necrotising and fatal cases; persistent severe pain warrants immediate discontinuation and investigation.
- Do not stop or rapidly reduce insulin when starting a GLP-1 medicine; stepwise adjustment with glucose monitoring prevents hyperglycaemia and ketoacidosis.
- GLP-1 medicines and tirzepatide are unsuitable during pregnancy and breastfeeding; tirzepatide can reduce oral-contraceptive reliability after initiation and dose escalation, so follow current MHRA advice.
- UK perioperative guidance generally continues these medicines but requires explicit disclosure, delayed-gastric-emptying and aspiration-risk assessment; follow the anaesthetist's current local plan.
Key red flags
Severe persistent epigastric pain that may radiate to the back, commonly with nausea or vomiting, needs immediate medicine cessation and urgent assessment; common nausea should not obscure this pattern.
Persistent vomiting or diarrhoea with reduced intake, postural symptoms or oliguria can cause acute kidney injury, particularly with diuretics, metformin, SGLT2 inhibitors or baseline CKD.
Right upper-quadrant pain, fever or jaundice during rapid weight loss suggests gallstones or cholecystitis and requires standard urgent biliary assessment rather than attributing all pain to injection nausea.
Ketones, weight loss, polyuria or marked hyperglycaemia after insulin reduction indicates that incretin therapy has not replaced essential insulin; urgent DKA-capable assessment may be needed.
Active nausea, vomiting, abdominal distension, severe reflux, gastroparesis or recent dose escalation raises concern for retained gastric contents despite fasting and needs anaesthetic planning.
Investigation priorities
Measure glycaemic response and guide co-therapy adjustment.
Management branches
Low-hypoglycaemia oral treatment is appropriate within NICE NG28.
- Review renal and hepatic function, heart failure, pancreatitis history, co-prescribed incretin therapy and the desired size of glucose reduction before selecting a specific agent.
- Use the current BNF dose for kidney function, explain that weight effect is neutral and reduce insulin or sulfonylurea only when glucose patterns justify it.
- Recheck HbA1c after enough time to demonstrate effect and stop or switch when the agreed target is not met rather than maintaining ineffective polypharmacy.
- Investigate severe abdominal pain, blistering skin disease or hypersensitivity promptly and report suspected serious reactions through MHRA Yellow Card.