The European Commission granted a marketing authorisation valid throughout the European Union for Glyxambi on 11 November 2016. Glyxambi is a diabetes medicine that contains two active substances, empagliflozin and linagliptin. Type 2 diabetes is a disease in which the body does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. The two active substances in Glyxambi work in different ways to lower glucose levels: empagliflozin works by blocking a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2); linagliptin is a dipeptidyl-peptidase-4 (DPP-4) inhibitor. Empagliflozin in combination with linagliptin (the same combination as in Glyxambi) was evaluated in 3 main studies involving 1,221 adults with type 2 diabetes. The main measure of effectiveness was the change after 24 weeks of treatment in the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled. The first study included patients whose blood glucose levels were not satisfactorily controlled with metformin and linagliptin. Patients were then given either empagliflozin or placebo in addition to their existing treatment.
Results showed that when empagliflozin was added to linagliptin and metformin, HbA1c levels decreased by 0.7-0.8 percentage points after 24 weeks, compared with no reduction when placebo was added. HbA1c levels were just below 8% at the start of the study. The second study included patients whose blood glucose levels were not satisfactorily controlled with metformin and empagliflozin. Adding linagliptin to treatment with empagliflozin and metformin for 24 weeks reduced HbA1c levels from 7.8% to 7.2%, compared with a reduction from 7.9% to 7.7% when placebo was added. A further study compared a fixed dose combination of empagliflozin and linagliptin (given in addition to metformin) with treatment with metformin plus either empagliflozin or linagliptin in patients who were not sufficiently controlled with metformin alone. The HbA1c levels were around 8% before treatment. After 24 weeks treatment the fixed dose combination reduced HbA1c levels to under 6.9% whereas they were around 7.3% with empagliflozin and linagliptin used alone. The most common side effects with Glyxambi are urinary infections. The most serious side effects are ketoacidosis, pancreatitis, hypersensitivity and hypoglycemia.