empagliflozin + linagliptin: clinical use

Prescribing considerations

• Confirm that the patient meets the combination product's restricted type 2 diabetes indication rather than an empagliflozin-only cardiorenal indication.
• Assess renal function, volume status and factors predisposing to ketoacidosis before initiation.
• Consider hypoglycaemia risk where insulin or a sulfonylurea is continued.
• Use caution with previous pancreatitis, restricted intake, dehydration, alcohol misuse, hypotension or medicines that promote fluid loss.

Contraindications and cautions

• Hypersensitivity to either active ingredient, another SGLT2 inhibitor, another DPP-4 inhibitor or a listed excipient.
• Do not use for type 1 diabetes.
• Do not use in end-stage renal disease or during dialysis; it is also not recommended below its licensed renal-function threshold.
• Not recommended in severe hepatic impairment.

Monitoring

• Renal function before treatment, periodically thereafter and before adding medicines that may impair renal function.
• Glycaemic control and hypoglycaemia risk, particularly with insulin or sulfonylureas.
• Volume status, blood pressure and electrolytes where fluid loss or hypotension is a concern.
• Ketones during major surgery or acute serious illness; blood testing is preferred.
• Investigate symptoms of ketoacidosis, pancreatitis, complicated urinary infection, bullous pemphigoid or Fournier's gangrene promptly.
• Urinary glucose is expected; the 1,5-anhydroglucitol assay is unreliable during SGLT2-inhibitor treatment.

Clinical pharmacology

Empagliflozin inhibits renal SGLT2, increasing urinary glucose and sodium excretion. Linagliptin inhibits DPP-4, prolonging GLP-1 and GIP activity and producing glucose-dependent increases in insulin with reduced glucagon. Exposure from the fixed combination is equivalent to taking the individual components together.

Formulation and product differences

• Film-coated tablets combine a fixed linagliptin content with either a lower or higher empagliflozin strength.
• The lower-empagliflozin tablet is pale yellow; the higher-empagliflozin tablet is pale pink. Both are arc-triangular and should be swallowed whole.

Tablet

Route: Oral

Strengths: 10 mg + 5 mg, 25 mg + 5 mg