Jentadueto XR

The FDA has approved Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets (by Boehringer Ingelheim and Eli Lilly and Company) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) when treatment with both linagliptin and metformin is appropriate. The approval carries the limitations that Jentadueto XR should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis and that the product has not been studied in patients with a history of pancreatitis.¹ An estimated 29 million Americans have diabetes, 28% of whom have not been given a diagnosis. T2D accounts for 90% to 95% of all diagnosed cases in the United States.²

PHARMACOLOGY

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It increases concentrations of active incretin hormones to stimulate the release of insulin in a glucose-dependent manner and decreases levels of circulating glucagon. 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

Jentadueto XR should be given once daily with a meal, and the tablet must be swallowed whole. The dose should be individualized to the patient’s current medication regimen, with a maximum daily dose of linagliptin 5 mg and metformin 2000 mg. Prior to beginning treatment, renal function should be assessed. Jentadueto XR should not be used in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/ 1.73 m2 and should not be initiated in patients with an eGFR of 30 to 45 mL/min/1.73 m2. If eGFR falls below 45 mL/min/1.73 m2, the risks and benefits of continuing treatment should be evaluated. Discontinuation of treatment may be required at the time of, or prior to, iodinated contrast imaging procedures.¹

CLINICAL TRIALS

The safety and efficacy of Jentadueto XR was established based on the results of adequate and well-controlled studies of linagliptin and metformin co-administered in patients with T2D that was inadequately controlled with diet and exercise and in combination with treatment with sulfonylurea medications.^1,2 The studies consisted of linagliptin and metformin as initial combination therapy, linagliptin and metformin as initial combination therapy compared with linagliptin in treatment-naïve patients, linagliptin as add-on combination therapy in patients already using metformin, linagliptin and metformin compared with glimepiride and metformin, and linagliptin as add-on combination therapy with metformin and a sulfonylurea.¹

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Jentadueto XR carries a boxed warning regarding the risk of metformin-associated lactic acidosis. Risk factors include renal impairment, concomitant use of certain medications, age 65 years and older, radiologic studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, Jentadueto XR should be discontinued immediately and the patient hospitalized, with prompt hemodialysis. Jentadueto XR is contraindicated in patients with severe renal impairment; metabolic acidosis, including diabetic ketoacidosis; or a history of hypersensitivity reaction to linagliptin or metformin.

If pancreatitis is suspected, the medication should be discontinued immediately. When used in combination with an insulin secretagogue, a lower dose of the secretagogue may be required to reduce the risk of hypoglycemia. Because metformin may decrease vitamin B12 levels, hematologic parameters should be monitored annually. Patients using DPP-4 inhibitors have reported severe and disabling arthralgia.

As with other antidiabetic medications, Jentadueto XR has not been shown to reduce the risk of macrovascular complications. Premenopausal women should be counseled regarding the potential for an unintended pregnancy, as metformin may induce ovulation in some anovulatory women. Elderly patients should have their renal function checked more frequently. Jentadueto XR should not be used in patients with hepatic impairment.

Carbonic anhydrase inhibitors may increase the risk of lactic acidosis. Medications that are eliminated by renal tubular secretion may increase the accumulation of metformin. Patients should be advised to avoid excessive alcohol consumption while using Jentadueto XR. The efficacy of linagliptin may be reduced when administered in combination with a strong P-glycoprotein inducer or CYP 3A4 inducer.

The most common adverse reactions (≥5% incidence) were nasopharyngitis and diarrhea.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.

References:

1. Jentadueto XR [package insert]. Boehringer Ingelheim; 2016. Accessed September 2016.

2. US FDA approves once-daily Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets for adults with type 2 diabetes. Lilly website. investor.lilly.com/releasedetail.cfm?releaseid=973469. Accessed September 2016.