title: The oral DPP-4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of linagliptin in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  After screening and a 14-day washout, subjects received linagliptin 2.5, 5 or 10 mg or placebo once-daily for 28 days in this randomized, double-blind, parallel, placebo-controlled within-dose groups study.
  
  
  RESULTS
  Seventy-seven patients entered the study (linagliptin: 61; placebo: 16). Four patients withdrew prematurely. There was little evidence of linagliptin accumulation. Exposure, maximum and trough plasma concentrations of linagliptin increased less than dose-proportionally. Rapid and sustained inhibition of dipeptidyl peptidase-4 reached 91-93% across linagliptin doses at steady state. At the end of the 24-h dosing interval, inhibition was still high (82-90%). There were marked increases in plasma glucagon-like peptide-1 after 28 days of dosing. Compared to placebo, all linagliptin doses resulted in statistically significant decreases of the area under the glucose curve following a meal tolerance test on day 29, that is, 24 h after the last study drug intake. After 28 days of treatment with linagliptin the placebo-corrected mean change in haemoglobin A1c (HbA1c) (median baseline 7.0%) was -0.31% (2.5-mg dose), -0.37% (5-mg dose) and -0.28% (10-mg dose). The frequency of adverse events was similar for linagliptin (31%) and placebo (34%). There were no notable safety concerns.
  
  
  CONCLUSIONS
  Linagliptin administration led to attenuation of postprandial glucose excursions and, despite a low HbA1c at baseline, statistically significant reductions in HbA1c after only 4 weeks of treatment. Linagliptin had a safety and tolerability profile similar to placebo in T2DM patients.
authors.affiliation: Institut für Klinische Forschung und Entwicklung GmbH, Mainz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.forename: B
authors.initials: B
authors.lastname: Uhlig-Laske
authors.forename: A
authors.initials: A
authors.lastname: Ring
authors.forename: A
authors.initials: A
authors.lastname: Ritzhaupt
authors.forename: U
authors.initials: U
authors.lastname: Graefe-Mody
authors.forename: K A
authors.initials: KA
authors.lastname: Dugi
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019518:Postprandial Period / Q000187:drug effects; D011687:Purines / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D010919:Placebos; D011687:Purines; D011799:Quinazolines