SGLT2 inhibitor + biguanide Pregnancy: When the patient plans to become pregnant, and during pregnancy, it is recommended that diabetes is not treated with this medicinal product but that insulin be used to maintain blood glucose as close to normal as possible. There are no data with empagliflozin in pregnant women; animal studies have shown adverse effects on postnatal development. Should not be used during breast-feeding (metformin is excreted into human milk; animal data show excretion of both substances in milk).

Empagliflozin with metformin

Brand names: Synjardy

Used in: Diabetes & DKA

A fixed-dose oral combination of empagliflozin, an SGLT2 inhibitor, with metformin, a biguanide, used for type 2 diabetes when both components are suitable.

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: One tablet twice daily in adults with normal renal function (eGFR >= 90 mL/min/1.73 m2); for patients insufficiently controlled on metformin the recommended starting dose provides empagliflozin 5 mg twice daily (10 mg total daily dose) with a metformin dose similar to that already being taken

Route: Oral

Frequency: Twice daily, with meals

Max: Empagliflozin 25 mg total daily dose; metformin maximum daily dose 3000 mg where eGFR >= 60 mL/min/1.73 m2 (2000 mg where eGFR 45 to < 60; 1000 mg where eGFR 30 to < 45) - §4.2 Table 1. The dosage should not exceed the maximum recommended daily dose of metformin.

UK SPC (Synjardy 12.5 mg/1,000 mg film-coated tablets) §4.2. The dosage should be individualised on the basis of the patient's current regimen, effectiveness and tolerability, using a recommended daily dose of 10 mg or 25 mg of empagliflozin. In patients tolerating a total daily dose of empagliflozin 10 mg who need tighter glycaemic control the dose can be increased to a total daily dose of 25 mg. When used with a sulphonylurea and/or insulin, a lower dose of sulphonylurea and/or insulin may be required to reduce the risk of hypoglycaemia. Patients switching from separate tablets should receive the same daily dose of empagliflozin and metformin already being taken, or the nearest therapeutically appropriate metformin dose. Missed dose: take as soon as remembered, but do not take a double dose at the same time - skip the missed dose. Hepatic impairment: must not be used. Elderly: use with caution; monitor renal function to help prevent metformin-associated lactic acidosis; in patients 75 years and older an increased risk of volume depletion should be taken into account. If no adequate strength of the fixed combination is available, individual monocomponents should be used instead. Take twice daily with meals to reduce metformin-associated gastrointestinal reactions; swallow tablets whole with water; continue diet with adequate distribution of carbohydrate intake, and an energy-restricted diet in overweight patients. PAEDIATRIC: the SPC gives a paediatric paragraph but no per-kg dose - dosage should be individualised; if empagliflozin is added to existing metformin the metformin dose should remain the same; the recommended empagliflozin starting dose is 5 mg twice daily (10 mg total daily dose), increasing to 12.5 mg twice daily (25 mg total daily dose) in patients tolerating 5 mg twice daily who require additional glycaemic control; the maximum recommended daily dose is 25 mg empagliflozin and 2000 mg metformin. No data are available for children with eGFR < 60 mL/min/1.73 m2 or below 10 years of age. Verify any paediatric use against a children's formulary.

Dose adjustments

Renal

eGFR should be assessed before initiation and at least annually thereafter; more frequently (e.g. every 3-6 months) in patients at increased risk of progression of renal impairment and in the elderly. §4.2 Table 1: eGFR >= 60 mL/min/1.73 m2 - metformin maximum daily dose 3000 mg (dose reduction may be considered as renal function declines), empagliflozin initiate 10 mg and may increase to 25 mg; eGFR 45 to < 60 - metformin maximum daily dose 2000 mg with a starting dose of at most half the maximum, empagliflozin initiate with 10 mg (patients with type 2 diabetes and established cardiovascular disease) or continue 10 mg if already taking empagliflozin; eGFR 30 to < 45 - metformin maximum daily dose 1000 mg with a starting dose of at most half the maximum, empagliflozin as for the 45 to < 60 band; eGFR < 30 - metformin is contraindicated and empagliflozin is not recommended. For cardiovascular risk reduction as add-on to standard of care, empagliflozin 10 mg daily should be used where eGFR is below 60 mL/min/1.73 m2.

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 (eGFR < 30 mL/min/1.73 m2)
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 when used with sulphonylurea or insulin (common)
Gastrointestinal symptoms - nausea, vomiting, diarrhoea, abdominal pain and loss of appetite (very common; most frequent on initiation and usually resolve spontaneously); constipation (common)
Genital infections - vaginal moniliasis, vulvovaginitis, balanitis (common); urinary tract infection including pyelonephritis and urosepsis (common); necrotising fasciitis of the perineum / Fournier's gangrene (very rare)
Increased urination (common); dysuria (uncommon); thirst (common); volume depletion (uncommon); blood creatinine increased / glomerular filtration rate decreased (uncommon)
Vitamin B12 decrease/deficiency (common); taste disturbance (common); lactic acidosis (very rare); diabetic ketoacidosis (rare)
Pruritus (generalised) and rash (common); urticaria, angioedema, erythema (uncommon); liver function test abnormalities and hepatitis (uncommon/rare)

Interactions

Sulphonylurea and/or insulin (§4.2) - a lower dose may be required to reduce the risk of hypoglycaemia
Medicinal products that can acutely impair renal function, such as antihypertensives, diuretics and NSAIDs (§4.4) - should be initiated with caution in metformin-treated patients (risk of metformin accumulation and lactic acidosis)
Excessive alcohol intake and concomitant medicinal products that may cause lactic acidosis (§4.4) - additional risk factors for lactic acidosis
Note: §4.5 was not captured in the fetched bundle - full interaction data must be verified against the SPC

Clinical monograph

How it works

Empagliflozin increases urinary glucose excretion through SGLT2 inhibition, while metformin reduces hepatic glucose production and improves peripheral insulin sensitivity.

Prescribing in practice

The most important safety point is risk of euglycaemic diabetic ketoacidosis from empagliflozin and lactic acidosis from metformin; withhold during acute illness, dehydration, sepsis, or surgery (sick-day rules) and avoid in significant renal impairment.
Empagliflozin predisposes to genital mycotic and urinary infections and rare Fournier's gangrene, and volume depletion may occur, particularly in the elderly or those on diuretics.
Both components have renal-function thresholds governing initiation and continuation, so confirm renal function before starting and periodically thereafter.

Monitoring

Monitor renal function, HbA1c, volume status and weight, with vigilance for ketoacidosis even when blood glucose is near-normal.

Counselling the patient

Stop the tablets and seek urgent advice if you become acutely unwell, dehydrated, or develop nausea, vomiting, abdominal pain, or breathlessness.
Maintain good genital hygiene and report any genital soreness or itching.
Take with food to reduce stomach upset from the metformin component.

Evidence & guidelines

NICE recommends SGLT2 inhibitors in type 2 diabetes, with empagliflozin's cardiovascular and renal benefits shown in EMPA-REG OUTCOME and subsequent trials.

Reference: NICE NG28; MHRA; ADA-EASD; 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