What is linagliptin?
Linagliptin (BI-1356 Brand Name: Trajenta®) is a drug for oral treatment of type 2 diabetes. In August 2011, the European Commission granted marketing authorization for the developed by the pharmaceutical company Boehringer Ingelheim drug. Linagliptin is a drug from the group of the dipeptidyl peptidase-4 inhibitors. These inhibit the enzyme dipeptidyl peptidase 4 (DPP-4).
Pharmacology
Pharmacodynamics (mode of action)
Linagliptin is an inhibitor of DPP-4 Dipeptylpeptidase isoenzyme which it competitive and selective against other isozymes as Dipeptylpeptidasen DPP-8 and DPP-9 inhibits. As Dipeptylpeptidase-4 inhibitor, it inhibits the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1). Compared to the 2008 already commercially used Gliptinen sitagliptin, vildagliptin, saxagliptin and linagliptin are recorded in cell cultures and in animal experiments in rats by a higher potency and a longer duration of action.
Pharmacokinetics
Many pharmacokinetic properties of linagliptin, such as clearance and volume of distribution, are non-linear and dose-dependent. The oral bioavailability of 10 mg linagliptin is 30%. In the organism, linagliptin is bound by its target protein, the Dipeptylpeptidase-4 and metabolized only to a small percentage. The elimination half-life is independent of dose and is 125-140 hours. Excretion is predominantly via the gastrointestinal tract. About 5% of the orally administered dose is excreted by the kidney. Thus, linagliptin is the only one approved to 2011 DPP4 inhibitor that can be given independent of renal function.
Admission / health policy
In August 2011, linagliptin was approved by the European Commission. The tablet is approved at a dose of 5 mg as monotherapy in type 2 diabetes mellitus, when there is an intolerance for metformin or metformin is contraindicated due to renal failure. If required, the combination of linagliptin with metformin, and the combination of linagliptin with metformin and sulfonylurea is approved.
In Germany has not yet brought the drug manufacturer Boehringer Ingelheim and its alliance partner Eli Lilly on the market in connection with the early benefit assessment by the Institute for Quality and Efficiency in Health Care (IQWiG). For the early benefit assessment, the manufacturer submitted in 2011 not the comparison with the standard therapy with metformin and sulfonylureas one, but compared linagliptin with other Gliptinen. The Institute for Quality and Efficiency in Health Care for linagliptin was therefore no additional benefit compared to the standard therapy with metformin and sulfonylureas certify. The Federal Joint Committee acknowledged the manufacturer the possibility to get at a later time a new benefit assessment of the active substance basis of a full valuation Langen. After another benefit assessment in December 2012, the Institute for Quality and Efficiency came in Health Care (IQWiG) concludes: Even in the evaluation of the new dossier no additional benefit of the drug compared with the appropriate comparator therapy can be ascertained. Because the manufacturer has not provided any relevant studies. Accordingly, the Federal Joint Committee has decided in February 2013 for technical reasons, that for linagliptin in both the monotherapy and dual combination therapy (linagliptin + metformin) an additional benefit is unsupported.