Boehringer Ingelheim and Eli Lilly received marketing authorization from the EC for linagliptin 5 mg film-coated tablets for the treatment of adults with type 2 diabetes. To be marketed under the trade name Trajenta® in Europe, the drug was sanctioned in combination with metformin and metformin plus sulfonylurea.
Linagliptin was previously approved for use as monotherapy in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to intolerance or contraindicated due to renal impairment. In the U.S. linagliptin 5 mg is marketed under the trade name Tradjenta™ and was approved in May to be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.
"Linagliptin is primarily excreted unmetabolized via bile and gut, meaning no dose adjustment is needed in adult patients with kidney or liver impairment," explains Anthony Barnett, professor of medicine and clinical director of the Department of Diabetes and Endocrinology, Heart of England NHS Foundation Trust, Birmingham, U.K. "This means that linagliptin is available at only one dose."
Klaus Dugi, corporate svp medicine, Boehringer Ingelheim, adds, "The Phase III clinical trial program has demonstrated efficacy with linagliptin in the treatment of adults with type 2 diabetes.” Studies have found that linagliptin reduces hemoglobin A1C (HbA1C or A1C) levels by a mean of -0.6 to -0.7%.
The approval of linagliptin in Europe was based on a clinical trial program that involved approximately 6,000 adults with type 2 diabetes. Included in the program were placebo-controlled studies evaluating linagliptin as monotherapy and in combination with metformin and/or sulfonylurea.
In two monotherapy studies, linagliptin showed a statistically significant mean difference in A1C from placebo of -0.6 to -0.7%. In patients who were not adequately controlled on metformin or metformin plus sulfonylurea, the addition of linagliptin also resulted in a statistically significant mean difference in A1C from placebo of -0.6%.
The incidence of hypoglycemia was similar to placebo and weight did not change significantly from baseline, the companies report. In the pooled analysis of the placebo-controlled trials, the overall incidence of adverse events in patients treated with placebo was similar to that seen with linagliptin (53.8% vs. 55%). The most frequently reported adverse reaction was hypoglycemia observed with the triple combination of linagliptin plus metformin plus sulfonylurea.