Companies: Boehringer Ingelheim and Lilly
Pharmacologic class: Dipeptidyl peptidase-4 (DPP-4) inhibitor
Active ingredient: Linagliptin 5 mg; tabs.
Indication: Adjunct to diet and exercise in type 2 diabetes mellitus, as monotherapy or combination therapy.
Pharmacology: Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation.
Clinical trials: Linagliptin was studied in 3,800 patients with type 2 diabetes in eight double-blind, placebo-controlled trials.
A total of 730 patients participated in two studies, one of 18-week and another of 24-week duration, to evaluate the efficacy and safety of linagliptin monotherapy. Treatment with linagliptin 5 mg daily provided statistically significant improvements in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), and two-hour postprandial glucose (PPG) compared with placebo.
A total of 701 patients participated in a 24-week study designed to assess the efficacy of linagliptin in combination with metformin. In combination with metformin, linagliptin provided statistically significant improvements in HbA1c, FPG, and two-hour PPG compared with placebo.
The efficacy of linagliptin is being evaluated in a 104-week double-blind, glimepiride-controlled noninferiority study in type 2 diabetic patients with insufficient glycemic control despite metformin therapy. After 52 weeks, linagliptin and glimepiride both had reductions from baseline in HbA1c (-0.4% for linagliptin, -0.6% for glimepiride) from a baseline mean of 7.7%.
A total of 389 patients participated in a 24-week study designed to assess the efficacy of linagliptin in combination with pioglitazone. In initial combination with pioglitazone 30 mg, linagliptin 5 mg provided statistically significant improvements in HbA1c and FPG compared with placebo with pioglitazone.
A total of 245 patients participated in an 18-week study designed to assess the efficacy of linagliptin in combination with a sulfonylurea. In combination with a sulfonylurea, linagliptin provided statistically significant improvements in HbA1c compared with placebo following 18 weeks of treatment; the improvements in FPG observed with linagliptin were not statistically significant compared with placebo.
A total of 1,058 patients participated in a 24-week study designed to assess the efficacy of linagliptin in combination with a sulfonylurea and metformin. In combination with a sulfonylurea and metformin, linagliptin provided statistically significant improvements in HbA1c and FPG compared with placebo.
Adults: 5 mg once daily.
Children: Not recommended.
Warnings/Precautions: Not for the treatment of type 1 diabetes or diabetic ketoacidosis. Pregnancy (Cat. B). Nursing mothers.
Interactions: Antagonized by strong P-gp or CYP3A4 inducers (e.g., rifampin); consider alternatives to linagliptin if used in combination. Concomitant sulfonylurea: may need lower dose of sulfonylurea to reduce risk of hypoglycemia. Concomitant insulin: not studied.
Adverse reactions: Nasopharyngitis, hypoglycemia, arthralgia, back pain, headache; hypersensitivity reactions (e.g., urticaria, angioedema, localized skin exfoliation, bronchial hyperreactivity), myalgia, pancreatitis.
How supplied: Tabs—30, 90, 1,000
For more information, call 800.542.6257 or visit www.Tradjenta.com.