DPP-4 inhibitor + biguanide Pregnancy: Should not be used during pregnancy. If the patient plans to become pregnant, or if pregnancy occurs, treatment should be discontinued and switched to insulin as soon as possible to lower the risk of foetal malformations associated with abnormal blood glucose levels. Metformin is excreted in human milk in small amounts; it is not known whether linagliptin is excreted into human milk - decide whether to discontinue breast-feeding or therapy.

Linagliptin with metformin

Brand names: Jentadueto

A fixed-dose oral combination of the DPP-4 inhibitor linagliptin and the biguanide metformin, taken twice daily with food to improve glycaemic control in adults with type 2 diabetes.

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: Patients inadequately controlled on the maximal tolerated dose of metformin monotherapy: usual starting dose provides linagliptin 2.5 mg twice daily (5 mg total daily dose) plus the dose of metformin already being taken. Dose should be individualised on the basis of the patient's current regimen, effectiveness and tolerability.

Route: Oral

Frequency: Twice daily, with meals (to reduce the gastrointestinal adverse reactions associated with metformin)

Max: 5 mg linagliptin plus 2,000 mg metformin hydrochloride per day (adults with normal renal function, GFR >= 90 mL/min)

SPC source: Jentadueto 2.5 mg/1,000 mg film-coated tablets; also available as 2.5 mg linagliptin plus 850 mg metformin hydrochloride. Patients switching from co-administration of linagliptin and metformin: initiate at the dose of linagliptin and metformin already being taken. Patients inadequately controlled on dual therapy with the maximal tolerated dose of metformin plus a sulphonylurea, or with insulin plus the maximal tolerated dose of metformin: linagliptin 2.5 mg twice daily (5 mg total daily dose) plus a dose of metformin similar to that already being taken; a lower dose of the sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia. All patients should continue a diet with adequate distribution of carbohydrate intake during the day; overweight patients should continue an energy-restricted diet. If a dose is missed it should be taken as soon as remembered, but a double dose should not be taken at the same time - in that case the missed dose should be skipped. Should not be used in patients with type 1 diabetes. Elderly: use with caution as age increases, since metformin is excreted by the kidney; monitoring of renal function is necessary to help prevent metformin-associated lactic acidosis. Hepatic impairment: not recommended (due to metformin); clinical experience is lacking. PAEDIATRIC: 'A clinical trial did not establish efficacy in paediatric patients 10 to 17 years of age. Therefore, treatment of children and adolescents with linagliptin is not recommended. Linagliptin has not been studied in paediatric patients under 10 years of age.' No paediatric dose is stated. Metformin should be temporarily discontinued in case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake). Not recommended in known or suspected mitochondrial disease (MELAS, MIDD) due to the risk of lactic acidosis exacerbation.

Dose adjustments

Renal

Assess GFR before initiation and at least annually thereafter; every 3-6 months in patients at increased risk of further progression of renal impairment and in the elderly. Review risk factors for lactic acidosis before initiating metformin in patients with GFR < 60 mL/min. Posology table: GFR 60-89 mL/min - metformin maximum daily dose 3,000 mg, dose reduction may be considered in relation to declining renal function; no linagliptin dose adjustment. GFR 45-59 - metformin maximum daily dose 2,000 mg, starting dose at most half of the maximum; no linagliptin dose adjustment. GFR 30-44 - metformin maximum daily dose 1,000 mg, starting dose at most half of the maximum; no linagliptin dose adjustment. GFR < 30 - metformin is contraindicated; no linagliptin dose adjustment. If no adequate strength of the fixed-dose combination is available, the individual monocomponents should be used instead.

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 the active substances or to any of the excipients
Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
Diabetic pre-coma
Severe renal failure (GFR < 30 mL/min)
Acute conditions with the potential to alter renal function, such as dehydration, severe infection, shock
Disease which may cause tissue hypoxia (especially acute disease or worsening of chronic disease), such as decompensated heart failure, respiratory failure, recent myocardial infarction, shock
Hepatic impairment, acute alcohol intoxication, alcoholism

Side effects

Hypoglycaemia (very common) - occurs when given together with a sulphonylurea (>= 1 case per 10 patients)
Abdominal pain (very common); diarrhoea (common, the most frequently reported reaction for linagliptin plus metformin at 1.6%); nausea (common)
Vitamin B12 decrease/deficiency (common); taste disturbance (common)
Lactic acidosis (very rare) - a serious metabolic complication, most often at acute worsening of renal function, cardiorespiratory illness or sepsis
Pancreatitis (rare); angioedema and urticaria (rare); hepatitis and erythema (very rare)

Interactions

Sulphonylureas and insulin - known to cause hypoglycaemia; caution advised and a dose reduction of the sulphonylurea or insulin may be considered
Intravascular iodinated contrast agents - may lead to contrast-induced nephropathy (metformin-related risk of lactic acidosis)
Medicinal products that can acutely impair renal function (antihypertensives, diuretics, NSAIDs) - initiate with caution in metformin-treated patients
Excessive alcohol intake and other medicinal products that may cause lactic acidosis - increased risk of lactic acidosis
NOTE: these entries are drawn from SPC §4.4; §4.5 (interactions) was not captured in the fetched source and still needs review

Clinical monograph

How it works

Linagliptin prolongs the action of incretin hormones to enhance glucose-dependent insulin release and suppress glucagon, while metformin reduces hepatic glucose output and improves peripheral insulin sensitivity.

Prescribing in practice

The metformin component carries the risk of lactic acidosis, so the combination is contraindicated in significant renal impairment, acute illness with hypoxia or dehydration, and must be withheld around iodinated contrast and major surgery.
Linagliptin is largely eliminated non-renally, but the combined product is still limited by metformin's renal cut-offs, so monitor eGFR and adjust or stop accordingly.
Hypoglycaemia is uncommon with these agents alone but increases when combined with a sulfonylurea or insulin, which may need dose reduction.

Monitoring

Monitor HbA1c, renal function and, with long-term metformin, vitamin B12 status, while remaining alert to symptoms of lactic acidosis.

Counselling the patient

Take with or just after food to reduce stomach upset from the metformin component.
Stop and seek advice during acute illness with dehydration, vomiting or before procedures using contrast dye.
Report any unexplained severe abdominal pain, as DPP-4 inhibitors have rarely been linked with pancreatitis.

Evidence & guidelines

DPP-4 inhibitor plus metformin combinations are recommended in NICE type 2 diabetes guidance as a step-up where metformin alone gives inadequate control, with single-tablet products aiding adherence.

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