New FDA Actions: Boehringer Ingelheim Pharmaceuticals, Inc and Eli Lilly and Co's Jentadueto

The FDA approved Jentadueto (linagliptin/metformin HCl) to help control blood sugar in adults with type 2 diabetes when treatment with both linagliptin and metformin is appropriate.

The FDA has approved Jentadueto (linagliptin/metformin hydrochloride) as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate.

The approval carries the limitations that Jentadueto is not to be used for the treatment of type 1 diabetes or diabetic ketoacidosis and that its use has not been studied in combination with insulin. Jentadueto carries a boxed warning regarding the risk for lactic acidosis.

Both linagliptin and metformin are commercially available as individual tablets. Jentadueto is marketed by Boehringer Ingelheim Pharmaceuticals, Inc and Eli Lilly and Company. It is available as 2.5 mg linagliptin/500 mg metformin, 2.5 mg linagliptin/850 mg metformin, and 2.5 mg linagliptin/1000 mg metformin.¹

Pharmacology and Pharmacokinetics

Linagliptin is a dipeptidyl peptidase-4 inhibitor. This inhibition results in an increased level of active incretin hormones, which stimulates the release of insulin in a glucose-dependent manner and decreases the level of circulating glucagon. Metformin decreases both hepatic glucose production and intestinal glucose absorption. It also improves insulin sensitivity by increasing glucose uptake and utilization in the periphery.

Age, gender, and race did not affect the pharmacokinetics of linagliptin. The clearance of metformin is decreased in elderly patients. Gender does not affect the pharmacokinetics of metformin. The effect of race on the pharmacokinetics of metformin has not been studied.¹

Dosage and Administration

The starting dose of Jentadueto should be individualized based on each patient’s current medication regimen. It should be given twice daily with meals. Dose increases, when appropriate, should be made gradually to minimize gastrointestinal side effects. The maximum daily dose of Jentadueto is 2.5 mg linagliptin/1000 mg metformin twice daily.

For patients who are not already using metformin, the starting dose of Jentadueto is 2.5 mg linagliptin/500 mg metformin twice daily. For patients already using metformin, the starting dose is 2.5 mg linagliptin with their current metformin dose twice daily. For patients already using both linagliptin and metformin, the individual components may be switched to Jentadueto at the same doses as each of the components.¹

Clinical Trials

A 24-week, randomized, double-blind, placebo-controlled study evaluated the role of linagliptin and metformin in 791 adults whose type 2 diabetes was inad- equately controlled by diet and exercise. The study found that hemoglobin A1C decreased by 1.6% in the group using 2.5 mg linagliptin/1000 mg metformin twice daily and increased by 0.1% in the placebo group.

Jentadueto has been shown to be bioequivalent to the commercially available formulations of linagliptin and metformin.²

Contraindications, Warnings, and Precautions

Jentadueto carries a boxed warning regarding the risk of lactic acidosis, which may occur due to metformin accumulation. This risk is increased in patients with renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. Symptoms include malaise, myalgias, respiratory distress, increased somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If lactic acidosis is suspected, immediately discontinue Jentadueto and hospitalize the patient.

Jentadueto is contraindicated in patients with renal impairment, metabolic acidosis (including diabetic ketoacidosis), and patients with a hypersensitivity to linagliptin or metformin.

Caution patients against excessive alcohol intake. Jentadueto should not be used in patients with hepatic impairment or hypoxic states. Confirm normal renal function before treatment and at least annually thereafter. Hold Jentadueto during radiologic studies with intravascular iodinated contrast materials or any surgical procedures that require decreased intake of fluids or food.

When Jentadueto is used concomitantly with a sulfonylurea, a lower dose of the sulfonylurea may be necessary to reduce the risk of hypoglycemia. Hematologic parameters should be monitored each year, as metformin may decrease vitamin B₁₂ levels. Antidiabetic medications, including Jentadueto, have not been shown to lower macrovascular risk. Jentadueto is Pregnancy Category B and should only be used in pregnancy if clearly needed. It should not be used during breast-feeding. Jentadueto is not approved for patients younger than 18 years. PT

Dr. Holmberg is a pharmacist who resides in Phoenix, Arizona.

References

1. Jentadueto complete prescribing information. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing Information/PIs/Jentadueto/Jentadueto.pdf. Accessed March 2012.

2. FDA approves Jentadueto (linagliptin/metformin hydrochloride) tablets for the treatment of adult patients with type 2 diabetes. http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2012/january_30_2012.html. Accessed March 2012.