GLP 1 Receptor Agonist Prescribing

Glucagon like peptide 1 receptor agonists stimulate glucose-dependent insulin release, suppress glucagon, slow gastric emptying and reduce appetite, giving substantial weight loss and cardiovascular benefit in selected agents. Tirzepatide combines GLP 1 and GIP receptor agonism. They are used for glucose control, weight management and cardiovascular risk reduction.

Hypoglycaemia. Minimal on their own; raised when combined with insulin or sulphonylureas.

Gastrointestinal effects. Nausea, vomiting and diarrhoea are dose dependent and settle with slow titration.

Indications. Type 2 diabetes with obesity or cardiovascular disease, type 2 diabetes with chronic kidney disease and albuminuria, and weight management where licensed.

Contraindications. Personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, and prior hypersensitivity. Avoid in pregnancy and in patients with severe gastroparesis.

Use with caution. History of pancreatitis, diabetic retinopathy (risk of early worsening when HbA1c falls quickly), gallstone disease, and patients at risk of dehydration.

Semaglutide (weekly subcutaneous). 0.25 mg once weekly for 4 weeks, then 0.5 mg weekly; if needed increase after 4 weeks to 1 mg, then 2 mg weekly for diabetes.

Semaglutide (oral). 3 mg once daily for 30 days, then 7 mg daily, increasing to 14 mg daily if needed. Take on an empty stomach with up to 120 mL of plain water, and wait 30 minutes before food, drink or other tablets.

Dulaglutide. 0.75 mg subcutaneously once weekly, increased to 1.5 mg after 4 weeks, then to 3 mg and 4.5 mg at 4 week intervals if needed.

Liraglutide. 0.6 mg subcutaneously once daily for 1 week, then 1.2 mg, then 1.8 mg daily if needed.

Tirzepatide. 2.5 mg subcutaneously once weekly for 4 weeks, then 5 mg; increase by 2.5 mg every 4 weeks to a maximum of 15 mg weekly.

Combination with other drugs. - With insulin or a sulphonylurea: reduce the insulin or sulphonylurea dose by 10 to 20% on starting. - With a DPP 4 inhibitor: stop the DPP 4 inhibitor. - With oral contraceptives: tirzepatide may reduce oral contraceptive effect, so use barrier contraception for 4 weeks after starting and after each dose increase.

Perioperative care. Delayed gastric emptying raises aspiration risk. Follow local anaesthetic advice about holding weekly agents for several days to 1 week before elective procedures, and use a liquid diet or full stomach precautions as advised.

Special groups. - Kidney impairment: no adjustment for most agents; monitor for dehydration and acute kidney injury during vomiting. - Liver disease: no adjustment for most agents; limited data in decompensated cirrhosis. - Pregnancy: stop at least 2 months before a planned pregnancy (semaglutide). - Breastfeeding: not advised. - Older adults: titrate slowly; watch for weight and muscle loss in frail patients.

Monitoring. HbA1c and weight at 3 months. Retinal screening before and during rapid HbA1c reduction. Heart rate and gastrointestinal symptoms at each titration step.

Stopping. Stop for suspected pancreatitis (severe persistent abdominal pain, with or without vomiting) and do not restart. Stop if there is no meaningful glucose or weight response by 6 months at the maximum tolerated dose.

Referral and escalation. Refer urgently for severe abdominal pain, signs of gallbladder disease, vision change, or a thyroid mass.