Synjardy

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Synjardy have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Synjardy are continuously monitored. Suspected side effects reported with Synjardy are carefully evaluated and any necessary action taken to protect patients.

In type 2 diabetes the body does not make enough insulin to control the level of glucose (sugar) in the blood or the body is unable to use insulin effectively. This leads to high blood levels of glucose. The two active substances in Synjardy, empagliflozin and metformin, work in different ways to lower blood glucose, and thus control disease symptoms.

Empagliflozin works by blocking a protein in the kidneys (called sodium-glucose co-transporter 2 or SGLT2). As blood is filtered by the kidneys, SGLT2 stops glucose in the bloodstream from being passed  into the urine. By blocking the action of SGLT2, empagliflozin causes more glucose to be removed in the urine, thereby reducing blood levels of glucose. Empagliflozin has been authorised in the EU under the trade name Jardiance since 2014.

Metformin works mainly by reducing the production of glucose in the body and reducing its absorption from the gut. Metformin has been available in the EU since the 1950s.

The benefits of empagliflozin in combination with metformin have been shown in three main studies involving 1,679 patients with type 2 diabetes whose blood sugar was not adequately controlled by metformin, alone or combined with other diabetes medicines (such as pioglitazone or a type of diabetes medicine called a sulphonylurea). The studies compared the effect of empagliflozin plus metformin versus placebo (a dummy treatment) with metformin. The main measure of effectiveness was the reduction in the blood level of a substance called glycosylated haemoglobin (HbA1c) after 24 weeks of treatment. HbA1c indicates how well blood glucose is controlled.

The studies showed a greater reduction in HbA1c when empagliflozin was given with metformin, compared with placebo given with metformin. Overall, the additional reduction was 0.58 percentage points with a lower dose and 0.62 percentage points with a higher dose, and these reductions were considered clinically relevant. Similar benefits were seen in the studies regardless of the other diabetes medicines being taken. In addition, the results indicated that the combination was associated with a beneficial decrease in body weight and blood pressure.

Supportive evidence was provided from several additional studies, including Results from some that were continuations of the main studies suggested the benefits of the combination continued with longer therapy. Studies also indicated Synjardy was as effective as empagliflozin and metformin taken separately, and that the combination helped reduce HbA1c when added to treatment including insulin.

Another main study showed that adding empagliflozin (one of the active substances of Synjardy) to usual treatment reduced adverse cardiovascular (heart and blood vessels) effects. The study involved patients with type 2 diabetes who already had cardiovascular disease (disease affecting the heart and blood vessels). The main measure of effectiveness was the occurrence of one of three major cardiovascular events: stroke, heart attack or death caused by cardiovascular disease. On average, patients in the study were followed up for 3.1 years. In those receiving empagliflozin, cardiovascular events occurred in 10.5% (490 out of 4,687) of patients compared with 12.1% (282 out of 2,333) of patients receiving placebo. Among these, in patients who were also taking metformin (the other active substance in Synjardy), the three major cardiovascular events occurred in 9.9% (344 out of 3,459) of patients receiving empagliflozin and in 10.9% (189 out of 1,734) of patients receiving placebo.

Another study compared adding empagliflozin to standard background therapy with diet and exercise, which included  metformin and/or insulin, in 158 children and adolescents aged 10 to 17 years of age with type 2 diabetes. When compared with placebo adding empagliflozin to background therapy for 26 weeks led to an additional reduction in HbA1c of 0.84 percentage points after 26 weeks of treatment.

For the full list of side effects and restrictions with Synjardy, see the package leaflet.

The most common side effects with Synjardy are hypoglycaemia (low blood sugar levels) when the medicine is taken with a sulphonylurea or insulin, infections of the urinary tract and genitals, and increased urination.

Synjardy must not be used in patients with:

• metabolic acidosis (when the body produces more acid than it gets rid of) or diabetic pre-coma (dangerous complications of diabetes);
• severely reduced kidney function or conditions that could affect the kidneys such as dehydration, severe infection or a steep fall in blood pressure;
• a condition that could reduce the supply of oxygen to body tissues (such as in patients with worsening heart failure, recent heart attack, breathing difficulty or a steep fall in blood pressure);
• liver impairment, or problems with alcoholism or alcohol intoxication.

The European Medicines Agency decided that Synjardy’s benefits are greater than its risks and recommended that it be approved for use in the EU for adults and children. The Agency concluded that the medicine could help produce a clinically meaningful reduction in blood glucose in patients with type 2 diabetes, and the benefits and risks were in line with those of the individual active substances. Synjardy was also shown to reduce cardiovascular events in patients with type 2 diabetes who already had cardiovascular disease. Because of concerns about the balance of benefit and risk in patients with reduced kidney function taking the fixed-dose combination, the agency recommended restricting its use in these patients.

Synjardy is available as tablets and can only be obtained with a prescription.

The recommended dose of Synjardy is one tablet twice a day with meals, and treatment is normally started with a tablet that supplies the dose of metformin the patient is already taking, together with the lowest dose of empagliflozin. Doses are adjusted based on the patient’s blood sugar levels.

If Synjardy is used in combination with insulin or a sulphonylurea (a medicine that increases the body’s production of insulin), the doses of these medicines may need to be lowered to avoid hypoglycaemia (low blood sugar levels).

For more information about using Synjardy, see the package leaflet or contact your doctor or pharmacist.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Synjardy’s benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded that the medicine could help produce a clinically meaningful reduction in blood glucose in patients with type 2 diabetes, and the benefits and risks were in line with those of the individual active substances. Synjardy was also shown to reduce cardiovascular events in patients with type 2 diabetes who already had cardiovascular disease. Because of concerns about the balance of benefit and risk in patients with reduced kidney function taking the fixed-dose combination, the CHMP recommended restricting its use in these patients.

The European Commission granted a marketing authorisation valid throughout the European Union for Synjardy on 27 May 2015.

Synjardy is a diabetes medicine used with diet and exercise to treat adults with type 2 diabetes. It contains the active substances empagliflozin and metformin. Synjardy is used:

• in patients whose diabetes is not sufficiently controlled by metformin alone;
• in combination with other diabetes medicines in patients whose diabetes is not sufficiently controlled on these medicines plus metformin;
• in patients who are already taking metformin and empagliflozin as separate tablets.