Efficacy and Safety of Linagliptin in 2681 Asian Patients Stratified by Age, Obesity, and Renal Function: A Pooled Analysis of Randomized Clinical Trials

INTRODUCTION Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations. RESULTS In the efficacy set, 1404 Asian patients received linagliptin [mean (standard deviation) age 54.5 (10.1) years; body mass index (BMI) 26.0 (3.9) kg/m2] and 661 received placebo [age 55.0 (9.7) years; BMI 26.1 (3.9) kg/m2] with the same glycated hemoglobin (HbA1c): 8.2 (0.9)% in both groups. At 24 weeks, the placebo-corrected adjusted mean ± standard error change from baseline in HbA1c with linagliptin was -0.73 ± 0.04% (95% confidence interval -0.81, -0.65; P < 0.0001). Reductions in HbA1c were similar upon stratification by age [<65 years, -0.71 ± 0.05% (-0.80, -0.62; P < 0.0001); ≥65 years, -0.81 ± 0.10% (-1.01, -0.60; P < 0.0001)], BMI (<25 kg/m2, -0.82 ± 0.06% [-0.94, -0.70; P < 0.0001]; ≥25 kg/m2, -0.65 ± 0.06% [-0.76, -0.54; P < 0.0001]) and estimated glomerular filtration rate [<90 mL/min/1.73 m2, -0.71 ± 0.06% (-0.82, -0.60; P < 0.0001); ≥90 mL/min/1.73 m2, -0.75 ± 0.06% (-0.87, -0.64; P < 0.0001)]. In the safety set (linagliptin, n = 1842; placebo, n = 839), 52.2% and 54.6% of patients, respectively, experienced adverse events. The rates of drug-related adverse events were 10.9% in the linagliptin group and 10.4% in the placebo group. The respective rates of hypoglycemia were 8.3% and 9.5%, mainly among patients treated with sulfonylurea or insulin. Severe hypoglycemia was rare (<1.0% in either group). CONCLUSION Linagliptin effectively reduced hyperglycemia in Asian patients with uncontrolled T2D, irrespective of age, BMI, renal function, or ethnic subgroups, and was well tolerated. FUNDING Boehringer Ingelheim, Eli Lilly and Company, and the Diabetes Alliance.