Boehringer Ingelheim Pharmaceuticals, Inc and Eli Lilly and Co's Tradjenta

The FDA approved Tradjenta (linagliptin) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Tradjenta (linagliptin) has received approval from the FDA as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus. The approval carries the limitations that Tradjenta should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis and that its use in combination with insulin has not been studied.¹ An estimated 25.8 million Americans have diabetes, with 90% to 95% of those cases being type 2 diabetes.² Tradjenta is marketed by Boehringer Ingelheim Pharmaceuticals, Inc, and Eli Lilly and Co.³

Pharmacology and Pharmacokinetics

Tradjenta 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.

Gender, age, and race did not affect the pharmacokinetics of Tradjenta. Tradjenta has not been studied in pediatric patients.

Dosing and Administration

Tradjenta is given as a 5-mg tablet to be administered once a day without regard to food.¹ No dose adjustment is required for patients with renal or hepatic impairment. ¹

Clinical Trials

Tradjenta has been studied as monotherapy and in combination with metformin, sulfonylurea (SU), metformin plus SU, and pioglitazone in patients with type 2 diabetes in double-blind, placebo-controlled trials.¹

The monotherapy trial evaluated 730 patients who were randomized to receive either Tradjenta or placebo for 18 or 24 weeks. The study found a statistically significant reduction in hemoglobin A1C of up to 0.7% in the Tradjenta arm compared with the placebo arm.

The metformin trial studied 701 patients who were randomized to use either Tradjenta plus metformin or placebo plus metformin for 24 weeks. A statistically significant reduction in hemoglobin A1C of 0.6% was found in the Tradjenta group compared with the placebo group.

The SU trial consisted of 245 patients who were randomized to receive either Tradjenta plus SU or placebo plus SU for 18 weeks. The study found a statistically significant reduction in hemoglobin A1C of 0.5% in the Tradjenta plus SU arm compared with the placebo plus SU arm.

The metformin plus SU trial involved 1058 patients randomized to use either Tradjenta plus metformin plus SU or placebo plus metformin plus SU for 24 weeks. At the study’s end, the Tradjenta plus metformin plus SU group displayed a statistically significant difference in reduction of hemoglobin A1C of 0.6% compared with the placebo plus metformin plus SU group.

The pioglitazone trial examined 389 patients who were randomized to use either Tradjenta plus pioglitazone or placebo plus pioglitazone for 24 weeks. The study found a statistically significant difference in reduction in hemoglobin A1C of 0.5% in the Tradjenta group compared with the placebo group. ^1,2

Contraindications, Warnings, and Precautions

Tradjenta is contraindicated in patients with a history of hypersensitivity reactions, such as urticaria, angioedema, or bronchial hyperreactivity, to Tradjenta or any of its components.

When Tradjenta is administered in combination with an insulin secretagogue, the rate of hypoglycemia may be higher than when Tradjenta is administered alone or with placebo. A lower dose of the insulin secretagogue may be necessary to minimize the risk of hypoglycemia. Clinical trials have not confirmed that treatment with Tradjenta or any other antidiabetic drug will reduce the risk of macrovascular complications.

Tradjenta is pregnancy category B; however, there are no adequate and wellcontrolled studies of its use in pregnant women and it should only be used during pregnancy if clearly needed. It is not known if Tradjenta is excreted into human milk and should be used cautiously in patients who are breast-feeding. Tradjenta should not be used in patients younger than 18 years.

Tradjenta’s efficacy may be reduced when it is concomitantly administered with an inducer of P-glycoprotein or cytochrome P450 3A4.

Nasopharyngitis was reported in ≥5% of patients using Tradjenta. The rate of pancreatitis was higher in patients randomized to use Tradjenta. ¹ Other adverse effects include muscle pain and headache. An FDA-approved Patient Package Insert, which explains its use and risks of treatment, will be dispensed with Tradjenta. ³ PT

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

References

1. Tradjenta complete prescribing information. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing Information/PIs/Tradjenta/Tradjenta.pdf. Accessed September 2011.

2. Boehringer Ingelheim and Lilly’s new type 2 diabetes treatment Tradjenta™ (linagliptin) tablets for adults now available in U.S. pharmacies. http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2011/june_15_2011.html. Accessed September 2011.

3. FDA approves new treatment for Type 2 diabetes. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm253501.htm. Accessed September 2011.