empagliflozin + metformin: clinical use

Prescribing considerations

• Confirm the indication is type 2 diabetes; this fixed combination is not licensed for type 1 diabetes.
• Assess renal function, hydration, ketoacidosis risk and metformin-associated lactic-acidosis risk before initiation.
• Interrupt treatment during major surgery or acute serious illness; use blood ketones when ketoacidosis monitoring is required.
• Review treatment during significant fluid loss, complicated urinary infection or before intravascular iodinated contrast.
• Consider increased volume-depletion risk in older people and those using diuretics or antihypertensives.

Contraindications and cautions

• Acute metabolic acidosis, including diabetic ketoacidosis or lactic acidosis
• Diabetic pre-coma
• Severe renal failure with eGFR below 30 mL/min/1.73 m²
• Acute dehydration, severe infection, shock or another condition liable to impair renal function
• Acute or worsening disease causing tissue hypoxia, including decompensated heart failure or respiratory failure
• Hepatic impairment, acute alcohol intoxication or alcoholism
• Hypersensitivity to either active ingredient or an excipient

Monitoring

• Renal function before treatment and periodically thereafter, with more frequent assessment when deterioration is likely
• HbA1c or other appropriate measures of glycaemic control; urine glucose is expected and the 1,5-anhydroglucitol assay is unreliable
• Volume status, blood pressure and electrolytes where dehydration is possible
• Blood ketones during major surgery, acute serious illness or suspected ketoacidosis
• Vitamin B12 when deficiency is suspected and periodically in people with risk factors
• Cardiac and renal function in stable chronic heart failure

Clinical pharmacology

Empagliflozin selectively inhibits renal SGLT2, increasing urinary glucose and sodium excretion. Metformin reduces hepatic glucose output and improves peripheral insulin sensitivity. The fixed-dose tablets are bioequivalent to the individual components taken together.

Formulation and product differences

• Four film-coated fixed combinations are licensed, differing in the relative amounts of empagliflozin and metformin.
• Tablet colour and markings distinguish the presentations.
• If the required fixed combination is unavailable, the individual components may be needed instead.