Long-acting insulin + GLP-1 agonist Pregnancy: No clinical experience in pregnant women. If a patient wishes to become pregnant, or pregnancy occurs, treatment should be discontinued. Should not be used during breast-feeding.

Insulin degludec with liraglutide

Brand names: Xultophy

A once-daily fixed-ratio subcutaneous injection combining the ultra-long-acting basal insulin degludec with the GLP-1 receptor agonist liraglutide, used to improve glycaemic control in adults with type 2 diabetes when an oral regimen is insufficient.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Add-on to oral glucose-lowering medicinal products: recommended starting dose 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide). One dose step contains 1 unit insulin degludec and 0.036 mg liraglutide. Dosed in accordance with the individual patient's needs; optimise glycaemic control via dose adjustment based on fasting plasma glucose.

Route: Subcutaneous injection into the thigh, upper arm or abdomen; rotate injection sites within the same region. Subcutaneous use only - must not be administered intravenously or intramuscularly, and must not be drawn from the cartridge of the pre-filled pen into a syringe.

Frequency: Once daily, at any time of the day but preferably at the same time each day. A minimum of 8 hours between injections should always be ensured.

Max: 50 dose steps daily (50 units insulin degludec and 1.8 mg liraglutide)

SPC source: Xultophy 100 units/mL + 3.6 mg/mL solution for injection. Pre-filled pen delivers 1 to 50 dose steps in one injection, in increments of one dose step. Transfer from a GLP-1 receptor agonist: discontinue the GLP-1 receptor agonist first; recommended starting dose 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) - the recommended starting dose should not be exceeded; if transferring from a long-acting (e.g. once-weekly) GLP-1 receptor agonist, start at the moment the next dose would have been taken. Transfer from any insulin regimen that includes a basal insulin component: discontinue the other insulin first; recommended starting dose 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) - should not be exceeded, but may be reduced to avoid hypoglycaemia in selected cases. Close glucose monitoring is recommended during transfer and in the following weeks. When added to sulfonylurea therapy, consider a reduction in the sulfonylurea dose. Missed dose: take upon discovery, then resume the usual once-daily schedule (respecting the 8-hour minimum interval). Dose adjustment may be needed with increased physical activity, dietary change or concomitant illness. Should not be used in type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Elderly (>=65 years): can be used; intensify glucose monitoring and adjust dose individually. Hepatic impairment: can be used in mild or moderate impairment with intensified glucose monitoring and individual dose adjustment; not recommended in severe hepatic impairment (liraglutide component). Paediatric population: 'There is no relevant use of Xultophy in the paediatric population.' Section 4.5 (interactions) was not captured in the fetched source; section 4.4 notes that cases of cardiac failure have been reported when pioglitazone was used in combination with insulin medicinal products.

Dose adjustments

Renal

Mild, moderate or severe renal impairment: glucose monitoring is to be intensified and the dose adjusted on an individual basis. Cannot be recommended for use in patients with end-stage renal disease.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to either or both active substances or to any of the excipients

Side effects

Hypoglycaemia (very common)
Gastrointestinal reactions - nausea, diarrhoea, vomiting, constipation, dyspepsia, gastritis, abdominal pain, gastro-oesophageal reflux disease, abdominal distension (common)
Decreased appetite (common); dizziness (common)
Injection site reaction (common); increased lipase and increased amylase (common)
Pancreatitis including necrotising pancreatitis (frequency unknown); cholelithiasis and cholecystitis (uncommon); anaphylactic reaction (frequency unknown)

Clinical monograph

How it works

Insulin degludec provides a flat, prolonged basal insulin effect by forming soluble multihexamers at the injection site, while liraglutide augments glucose-dependent insulin secretion, suppresses glucagon and slows gastric emptying.

Prescribing in practice

Because the components are in a fixed ratio, the insulin and GLP-1 doses cannot be titrated independently, so it must not be combined with another GLP-1 receptor agonist and dose adjustment is guided by the basal insulin requirement.
Initiate cautiously when switching from a previous basal insulin or GLP-1 agonist, reducing or stopping the prior agent to avoid stacking, and titrate gradually against fasting glucose.
Avoid in type 1 diabetes and diabetic ketoacidosis, and use with care in those with a history of pancreatitis or significant gastrointestinal disease.

Monitoring

Monitor fasting and overall glycaemic control alongside body weight, and review for hypoglycaemia and persistent gastrointestinal symptoms during titration.

Counselling the patient

Inject under the skin once daily at a consistent time and rotate sites to avoid lipohypertrophy.
Nausea is common at first and usually settles; report severe or persistent abdominal pain.
Carry a fast-acting carbohydrate in case of hypoglycaemia, especially if also taking a sulfonylurea.

Evidence & guidelines

Fixed-ratio basal insulin plus GLP-1 agonist combinations are recommended by NICE as an intensification option in type 2 diabetes, reducing HbA1c with less weight gain and hypoglycaemia than uptitrated basal insulin alone.

Reference: NICE NG28; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways