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15-03-2011 | Diabetes | Article

Linagliptin shows preliminary promise in Type 2 diabetes

Abstract

Free abstract

MedWire News: The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin has shown promise for controlling glucose levels in patients with Type 2 diabetes, results of a phase II study suggest.

Linagliptin is an orally available, potent, and long-acting nonpeptidomimetic DPP-4 inhibitor that is in clinical development. Unlike other DPP-4 inhibitors, it is excreted mainly through the feces rather than by the renal route, making it potentially useful in patients with renal impairment.

In the present study, Klaus Dugi (Boehringer Ingelheim Pharma GmbH & Co KG, Germany) and co-workers investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of linagliptin. The study subjects were 77 patients with Type 2 diabetes mellitus who were randomly assigned to take linagliptin 2.5, 5, or 10 mg, or placebo once-daily for 28 days.

Four patients withdrew prematurely from the study, report Dugi et al in the journal Diabetes, Obesity and Metabolism.

Analysis of the remaining 73 patients indicated that linagliptin did not accumulate in the body and that plasma levels of the drug increased in a less-than-dose-proportional manner. Inhibition of DDP-4 reached 91-93% at all linagliptin doses; inhibition was rapid and sustained throughout the 24-hour dosing interval.

Plasma levels of glucagon-like peptide-1 rose markedly between baseline and day 28 of linagliptin treatment. Furthermore, all linagliptin doses resulted in significant reductions in fasting plasma glucose, seven-point mean glucose, 2-hour postprandial glucose, plasma glucose area under the curve after a meal tolerance test, and glycated hemoglobin (HbA1c).

The mean HbA1c at baseline was 7.0%. The placebo-corrected reductions in HbA1c between baseline and day 28 were 0.31%, 0.37%, and 0.28% for the 2.5 mg, 5 mg, and 10 mg doses, respectively.

The frequency of adverse events was similar for linagliptin (31%) and placebo (34%), there were no major or minor hypoglycemic episodes, and there were no notable safety concerns, say the authors.

"Data from long-term studies will be needed to support the long-term effects of linagliptin as well as to fully understand the mechanism of the effects and determine whether its unique non-renal clearance pathway translates into clinical benefit over the DPP-4 inhibitors launched to date," Dugi et al conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Joanna Lyford