title: Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials.
abstract: We aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM).
  
  
  
  Data were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (-0.42% [±0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment interaction p = 0.0489). The proportion of patients with baseline HbA1c >7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05).
  
  
  
  This post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS.
authors.affiliation: University of Pisa, Pisa, Italy. Electronic address: stefano.delprato@med.unipi.it.
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.affiliation: Boehringer Ingelheim Ltd UK, Bracknell, Berkshire, UK.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Crowe
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000069476:Linagliptin; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human
keywords: Asian; Body mass index; DPP-4 inhibitor; Fasting plasma glucose; Linagliptin; Metabolic syndrome; Race; Type 2 diabetes