Synjardy has received FDA approval for an expanded indication to include treatment-naïve adults with type 2 diabetes
Synjardy (empagliflozin/metformin hydrochloride) tablets (by Boehringer Ingelheim and Eli Lilly and Company) has received FDA approval for an expanded indication to include treatment-naïve adults with type 2 diabetes (T2D). Synjardy is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D when treatment with both empagliflozin and metformin is appropriate. The approval carries the limitation that Synjardy should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis.1,2
Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, resulting in increased urinary glucose excretion. Metformin is a member of the biguanide class. It decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.1
Dosage and Administration
The starting dose of Synjardy should be individualized based on the patient’s current medication regimen, with a maximum daily dose of 12.5 mg empagliflozin/1000 mg metformin twice daily. To reduce the gastrointestinal side effects of metformin, the tablet should be taken with meals, with a gradual escalation in dose. Renal function should be assessed prior to initiation of treatment. Synjardy should not be used in patients with an eGFR below 45 ml/min/1.73m2. Discontinuation may be required at the time of, or prior to, iodinated contrast imagining procedures.1
The additional indication for Synjardy was based on a Phase III, double-blind, randomized, active-controlled study that evaluated the efficacy and safety of empagliflozin in combination with metformin as initial therapy compared with treatment with either empagliflozin or metformin alone. At 24 weeks, combination treatment displayed significant reductions in hemoglobin A1c as compared to treatment with either component alone.1,2
Contraindications, Warnings and Precautions
Synjardy carries a boxed warning regarding the risk of metformin-associated lactic acidosis. Risk factors include renal impairment, concomitant use of certain medications, age 65 or older, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, Synjardy should be discontinued immediately and the patient hospitalized, with prompt hemodialysis recommended.
Synjardy is contraindicated in patients with moderate to severe renal impairment, end-stage renal disease, or dialysis; metabolic acidosis, including diabetic ketoacidosis; or history of serious hypersensitivity to empagliflozin or metformin.
Patients should be assessed for hypotension before initiation of treatment, especially those who have renal impairment, are elderly, have low systolic blood pressure, or are concurrently using diuretics. Renal function should be monitored throughout treatment with Synjardy. Patients should be evaluated for signs and symptoms of urinary tract infections and treated promptly, if indicated. When used in combination with insulin or an insulin secretagogue, a lower dose of the insulin or secretagogue may be required to minimize the risk of hypoglycemia. Patients should be monitored for genital mycotic infections and treated, if appropriate. Metformin may lower vitamin B12 levels; hematologic parameters should be monitored yearly. Increased LDL-C may occur during treatment with empagliflozin; it should be monitored and managed, as appropriate. As with other antidiabetic medications, Synjardy has not been shown to reduce the risk of macrovascular complications.
Concomitant use with carbonic anhydrase inhibitors may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion may increase the accumulation of metformin. Alcohol may potentiate the effect of metformin on lactate metabolism, so patients should be cautioned against excessive alcohol intake.
Synjardy should not be used in the second or third trimester of pregnancy or during breast-feeding. Premenopausal women should be counseled regarding the potential for an unintended pregnancy because metformin may induce ovulation in some anovulatory women. Elderly patients should have their renal function checked more frequently. Synjardy should not be used in patients with hepatic impairment.
The most common adverse reactions associated with empagliflozin (5% or greater incidence) are urinary tract infections and female genital mycotic infections. The most common adverse reactions associated with metformin (greater than 5% incidence) are diarrhea, nausea or vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.1
Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.
- Synjardy [prescribing information]. Ridgefield, CN: Boehringer Ingelheim Pharmaceuticals, Inc;2016. docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Synjardy/Synjardy.pdf. Accessed November 30, 2016.
- U.S. FDA expands indication for type 2 diabetes treatment Synjardy (empagliflozin/metformin hydrochloride) to include treatment-naïve adults [news release]. Ridgefield, CN, and Indianapolis, IN: PRNewswire; July 19, 2016. investor.lilly.com/releasedetail.cfm?ReleaseID=980079. Accessed November 30, 2016.