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DPP-4 + biguanide Pregnancy: Should not be used during pregnancy — no adequate data for sitagliptin in pregnant women (animal reproductive toxicity at high doses); limited data suggest metformin is not associated with an increased risk of congenital malformations. If a patient wishes to become pregnant or a pregnancy occurs, discontinue and switch to insulin as soon as possible. Must not be used while breast-feeding (a contraindication).

Sitagliptin with metformin

Brand names: Janumet

Used in: Diabetes & DKA

This fixed-dose combination tablet for type 2 diabetes combines the DPP-4 inhibitor sitagliptin with the biguanide metformin, used when control on a single agent is inadequate.

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: Individualised on the basis of the patient's current regimen, effectiveness and tolerability, not exceeding the maximum recommended daily dose of 100 mg sitagliptin. For patients inadequately controlled on the maximal tolerated dose of metformin monotherapy the usual starting dose should provide sitagliptin 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken
Route: Oral
Frequency: Twice daily with meals (to reduce the gastrointestinal adverse reactions associated with metformin)
Max: Sitagliptin 100 mg daily; metformin maximum daily dose 3000 mg (at GFR 60-89 mL/min) — see renal adjustment for lower limits
UK SPC for Janumet 50 mg/1000 mg film-coated tablets (fixed-dose combination — both components covered by this label). Patients switching from co-administration of sitagliptin and metformin: initiate at the dose of sitagliptin and metformin already being taken. Patients inadequately controlled on dual therapy with maximal tolerated metformin plus a sulphonylurea, plus a PPAR-gamma agonist, or plus insulin: the dose should provide sitagliptin 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to that already being taken; a lower dose of the sulphonylurea or of insulin may be required to reduce the risk of hypoglycaemia. All patients should continue their recommended diet with an adequate distribution of carbohydrate intake during the day. Hepatic impairment: must not be used. Elderly: use with caution as age increases; monitor renal function to help prevent metformin-associated lactic acidosis. Paediatric population: should not be used in children and adolescents 10 to 17 years of age because of insufficient efficacy; has not been studied under 10 years of age. If no adequate strength of the fixed combination is available, the individual monocomponents should be used instead. SOURCE GAP: section 4.5 (interactions) was not captured in the fetched bundle — clinician to check the full SPC for interaction data.

Dose adjustments

Renal

Assess GFR before initiation and at least annually (every 3-6 months if at increased risk of progression or elderly). GFR 60-89 mL/min: metformin maximum daily dose 3000 mg (dose reduction may be considered as renal function declines); sitagliptin maximum 100 mg daily. GFR 45-59: metformin maximum 2000 mg daily with a starting dose at most half the maximum; sitagliptin maximum 100 mg daily. GFR 30-44: metformin maximum 1000 mg daily with a starting dose at most half the maximum; sitagliptin maximum 50 mg daily. GFR under 30: metformin is contraindicated; sitagliptin maximum 25 mg daily. The maximum daily dose of metformin should preferably be divided into 2-3 daily doses.

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 under 30 mL/min)
  • Acute conditions with the potential to alter renal function: dehydration, severe infection, shock, intravascular administration of iodinated contrast agents
  • Acute or chronic disease which may cause tissue hypoxia: cardiac or respiratory failure, recent myocardial infarction, shock
  • Hepatic impairment; acute alcohol intoxication, alcoholism; breast-feeding

Side effects

  • Hypoglycaemia (common; 13.8% with sulphonylurea and 10.9% with insulin)
  • Nausea, vomiting, flatulence (common)
  • Vitamin B12 decrease/deficiency (common)
  • Diarrhoea, constipation, upper abdominal pain, somnolence, pruritus (uncommon)
  • Acute pancreatitis, including fatal and non-fatal haemorrhagic and necrotising pancreatitis (frequency not known)
  • Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis and Stevens-Johnson syndrome (frequency not known); thrombocytopenia (rare)

Interactions

  • Iodinated contrast agents (intravascular) — contraindicated acute condition with the potential to alter renal function
  • Medicinal products that can acutely impair renal function (antihypertensives, diuretics, NSAIDs) — initiate with caution in metformin-treated patients
  • Sulphonylureas and insulin — increased risk of hypoglycaemia; a lower dose of the sulphonylurea or insulin may be required
  • Alcohol — excessive intake is a risk factor for lactic acidosis; acute alcohol intoxication and alcoholism are contraindications
  • Note: section 4.5 was not captured in the fetched bundle — the above are drawn from sections 4.2, 4.3 and 4.4

Clinical monograph

How it works

Sitagliptin inhibits DPP-4 to prolong incretin action, enhancing glucose-dependent insulin secretion and suppressing glucagon, while metformin lowers hepatic glucose output and improves insulin sensitivity.

Prescribing in practice

  • The metformin component requires renal function review and temporary withholding during acute illness, dehydration, or before iodinated contrast procedures, owing to the rare risk of lactic acidosis.
  • Sitagliptin may rarely precipitate acute pancreatitis and hypersensitivity reactions; discontinue if pancreatitis is suspected.
  • Metformin frequently causes gastrointestinal side effects, reduced by taking with food and considering a modified-release preparation.

Monitoring

Monitor renal function and HbA1c, with review of gastrointestinal tolerance and any features suggesting pancreatitis.

Counselling the patient

  • Take with or after food to limit stomach upset.
  • Stop temporarily and seek advice if you become severely unwell or dehydrated, or before a contrast scan.
  • Report severe or persistent abdominal pain to your team.

Evidence & guidelines

NICE positions metformin as first-line therapy for type 2 diabetes, with DPP-4 inhibitors such as sitagliptin as established options for treatment intensification.

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).

Related

Curated clinical cross-links plus same-class fallbacks.

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