Linagliptin

IUPAC: 8 - [ (3R )-3- aminopiperidine -1-yl ] -7 - ( but-2 -in-1 -yl ) -3 - methyl-1- [(4- methylquinazolin -2-yl ) methyl] -3,7- dihydro-1H -purine -2 ,6- dione

A10BH05

Antidiabetics

DPP4 inhibitor

Template: Infobox chemical / molecular formula search available

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 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 to inhibit degradation of the incretin hormone glucagon-like peptide 1 (GLP -1). Compared to the 2008 already commercially used Gliptinen sitagliptin, saxagliptin and vildagliptin to linagliptin recorded in cell cultures and in animal experiments in rats by a higher potency and longer duration of action.

Pharmacokinetics

Many pharmacokinetic properties of linagliptin 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 dose-independent and is 125-140 hours. Excretion is predominantly via the gastrointestinal tract. About 5 % of the orally administered dose is excreted in urine. Thus, linagliptin is the only one approved to 2011 DPP4 inhibitor that can be given independent of renal function.

Approval / 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 incompatibility of metformin or metformin is contraindicated due to renal insufficiency. If necessary, 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 to 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 comparisons 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 granted the producers the opportunity to get at a later date re- benefit assessment of the active substance basis of a full valuation Langen. After re- benefit assessment in December 2012, the Institute for Quality and Efficiency came in Health Care ( IQWiG) to the result: Even in the evaluation of new dossiers, no additional benefit of the drug compared to the appropriate comparator therapy can be ascertained. Because the manufacturer did not provide relevant studies. Accordingly, the Federal Joint Committee decided in February 2013 for technical reasons, that for linagliptin in both the monotherapy and dual combination therapy ( linagliptin metformin) an additional benefit had not been established.