title: Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial.
abstract: Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (⩽54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and -0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ⩽1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies.
authors.affiliation: Diabetes Centre Bad Lauterberg, Bad Lauterberg im Harz, Germany Division of Diabetology, Medical Department I, St. Josef-Hospital (Ruhr-University Bochum), Bochum, Germany michael.nauck@rub.de.
authors.forename: Michael Albrecht
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: di Domenico
authors.affiliation: Boehringer Ingelheim Ltd, Bracknell, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Kobe
authors.affiliation: Boehringer Ingelheim Ltd, Bracknell, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Toorawa
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005060:Europe; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069476:Linagliptin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D013607:Tablets; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D000077205:Pioglitazone; D013607:Tablets; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human
keywords: Linagliptin; efficacy; pioglitazone; safety; single-pill combination; type 2 diabetes