Institution: | 1.Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Ministry of Health,Shanghai,China;2.Seth Gordhandas Sunderdas, Medical College and King Edward Memorial Hospital,Mumbai,India;3.Boehringer Ingelheim Pharma GmbH & Co. KG,Ingelheim,Germany;4.Department of Medicine and Therapeutics,Hong Kong Institute of Diabetes and Obesity,Hong Kong,China;5.The Chinese University of Hong Kong, Prince of Wales Hospital,Hong Kong,China |
Abstract: | IntroductionAsian 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.MethodsData 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.ResultsIn 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).ConclusionLinagliptin effectively reduced hyperglycemia in Asian patients with uncontrolled T2D, irrespective of age, BMI, renal function, or ethnic subgroups, and was well tolerated.FundingBoehringer Ingelheim, Eli Lilly and Company, and the Diabetes Alliance. |