dapagliflozin + metformin: clinical use

Prescribing considerations

• Confirm that both component requirements can be supplied by the fixed combination; otherwise use separate components.
• Assess renal function, hydration, blood pressure and risk factors for ketoacidosis or lactic acidosis before initiation.
• Do not use for type 1 diabetes.
• Temporarily interrupt during dehydration, major surgery or acute serious illness; monitor blood ketones during hospital interruption.
• Withhold for intravascular iodinated contrast and around relevant anaesthesia, restarting only after oral intake and renal function are stable.
• Counsel about genital and urinary infections, foot care, sick-day management and ketoacidosis without marked hyperglycaemia.

Contraindications and cautions

• Hypersensitivity to either active ingredient or an excipient
• Acute metabolic acidosis, including diabetic ketoacidosis or lactic acidosis
• Diabetic pre-coma
• Severe renal failure with GFR below 30 mL/min
• Acute conditions liable to alter renal function, including dehydration, severe infection or shock
• Disease causing tissue hypoxia, such as acute cardiac or respiratory failure, recent myocardial infarction or shock
• Hepatic impairment
• Acute alcohol intoxication or alcoholism

Monitoring

• Assess GFR before treatment and at least annually; monitor more often in older people or those at risk of renal decline.
• The selected SmPCs advise against initiation below GFR 60 mL/min and discontinuation if GFR remains below 45 mL/min.
• Monitor volume status and blood pressure when dehydration or hypotension is a concern.
• Check blood ketones when ketoacidosis is suspected and during interruption for major surgery or acute serious illness.
• Consider vitamin B12 measurement when deficiency is suspected or risk factors are present.
• Use alternatives to the 1,5-anhydroglucitol assay for glycaemic assessment; positive urine glucose is expected.

Clinical pharmacology

Dapagliflozin selectively inhibits renal SGLT2, producing insulin-independent urinary glucose loss with mild osmotic diuresis. Metformin reduces hepatic gluconeogenesis, modestly improves peripheral insulin sensitivity and delays intestinal glucose absorption. The components do not meaningfully alter one another's pharmacokinetics.

Formulation and product differences

• Both selected products are immediate-release film-coated fixed-combination tablets.
• The selected generic and Xigduo tablets differ in appearance and markings; identify the product using the dispensed pack and leaflet.
• The fixed combination cannot adjust one component independently, so separate tablets may be required when component requirements differ.

Tablet

Route: Oral

Strengths: 5 mg + 1000 mg, 5 mg + 850 mg