Efficacy and safety of linagliptin in Asian patients with type 2 diabetes mellitus inadequately controlled by metformin: A multinational 24-week, randomized clinical trial.

BACKGROUND: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) in Asia, clinical trials for glucose-lowering therapies are often dominated by Caucasian and/or Western populations. The present Phase III randomized placebo-controlled double-blind, 24-week study evaluated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin added to metformin in Asian T2DM patients. METHODS: In all, 306 patients (n = 265 Chinese; n = 24 Malaysian; n = 17 Filipino), aged 18-80 years with HbA1c between ≥7.0 and ≤10.0% and on metformin therapy were randomized (2:1) to either linagliptin 5 mg daily or placebo added to metformin. Antidiabetes drugs other than metformin were washed out prior to randomization. The primary endpoint was change in mean HbA1c from baseline after 24 weeks. RESULTS: Baseline characteristics were well-matched between the groups (overall mean [±SD] HbA1c 8.0 ± 0.8%). Adjusted mean (±SE) HbA1c decreased in the linagliptin and placebo groups by -0.66 ± 0.05 and -0.14 ± 0.07%, respectively (placebo-corrected difference -0.52 ± 0.09%; 95% confidence interval [CI] -0.70, -0.34; P < 0.0001). In patients with baseline HbA1c ≥8.5%, the placebo-corrected decrease in HbA1c was -0.89 ± 0.17% (P < 0.0001). Adverse events occurred in similar proportions in the linagliptin and placebo patients (27.3% and 28.0%, respectively) and few were considered drug-related (2.4% and 0.0%, respectively). Hypoglycemia occurred in 1.0% of patients in both groups. Linagliptin therapy was weight neutral. CONCLUSIONS: Linagliptin 5 mg was efficacious and well tolerated over 24 weeks in Asian patients with T2DM inadequately controlled by metformin.

Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: A multinational, 24-week, randomized, clinical trial.

AIMS/INTRODUCTION: Asian patients represent a large portion of the global population with type 2 diabetes mellitus, but are underrepresented in trials of glucose-lowering therapies. The present randomized, phase III, placebo-controlled, double-blind, 24-week study evaluated the dipeptidyl peptidase-4 inhibitor, linagliptin, as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus. MATERIALS AND METHODS: Patients who were treatment naïve or had been treated with one oral antidiabetes drug were randomized to either linagliptin 5 mg daily or a placebo after washout. The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks. RESULTS: A total of 300 Asian (87% Chinese) patients with type 2 diabetes mellitus were randomized to linagliptin or placebo at a 2:1 ratio. After 24 weeks of treatment, adjusted mean (standard error) glycated hemoglobin decreased by a placebo-corrected -0.50 ± 0.11 (P < 0.0001). In patients with baseline glycated hemoglobin ≥8.5%, the placebo-corrected decrease in glycated hemoglobin was -0.91 ± 0.20% (P < 0.0001). Adverse events occurred in 28.0 and 28.3% of linagliptin and placebo patients, respectively, but few were drug-related (3.0 and 2.0%, respectively). Hypoglycemia was reported by one linagliptin patient and no placebo patients. Treatment with linagliptin was weight neutral. CONCLUSIONS: In Asian patients with inadequately controlled type 2 diabetes mellitus, linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks.