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Efficacy and safety of teneligliptin added to metformin in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin: A phase 3, randomized, double-blind, placebo-controlled study.
Ji, L, Li, L, Ma, J, Li, X, Li, D, Meng, B, Lu, W, Sun, J, Liu, Y, Takayanagi, G, et al
Endocrinology, diabetes & metabolism. 2021;(2):e00222
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Abstract
INTRODUCTION We evaluated the efficacy and safety of teneligliptin compared with placebo when added to metformin therapy in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy. METHODS This multicentre, randomized, double-blind, placebo-controlled, parallel-group study enrolled type 2 diabetes patients with glycosylated haemoglobin (HbA1c) 7.0%-<10.0% and fasting plasma glucose (FPG) <270 mg/dl, receiving a stable metformin dose ≥1000 mg/day. Teneligliptin 20 mg or placebo was administered orally once daily (qd) before breakfast for 24 weeks. The primary efficacy end-point was change in HbA1c from baseline to Week 24. Safety end-points included the incidence of adverse events (AEs). RESULTS The least square mean (LSM) change from baseline (standard error [SE]) was -0.72 (0.07) (95% confidence intervals [CI], -0.87, -0.58) for teneligliptin and -0.01 (0.07) (95% CI, -0.16, 0.13) for placebo. The differences (LSM ± SE) between the placebo and teneligliptin groups in HbA1c and FPG were -0.71% ± 0.11% (p < .0001) and -16.5 ± 4.7 mg/dl (p = .0005), respectively. Teneligliptin yielded significant changes in HbA1c (-0.81%; p < .0001) and FPG (-22.2 mg/dl; p < .0001) at Week 12. At Week 24, more patients achieved HbA1c <7.0% with teneligliptin (41.7%) compared with placebo (16.1%; p < .0001). Treatment-emergent AE incidence was similar with teneligliptin (58.9%) and placebo (68.3%); upper respiratory tract infection, hyperuricaemia and hyperlipidaemia were the most common AEs. CONCLUSIONS Teneligliptin 20 mg qd for 24 weeks added to ongoing metformin treatment significantly decreased HbA1c and FPG levels compared with placebo in Chinese type 2 diabetes patients. The combination was safe and tolerable.
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Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.
Weycker, D, Li, X, Wygant, GD, Lee, T, Hamilton, M, Luo, X, Vo, L, Mardekian, J, Pan, X, Burns, L, et al
Thrombosis and haemostasis. 2018;(11):1951-1961
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Abstract
In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64-0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71-0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70-0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.
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Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study.
Zhu, D, Gan, S, Liu, Y, Ma, J, Dong, X, Song, W, Zeng, J, Wang, G, Zhao, W, Zhang, Q, et al
The lancet. Diabetes & endocrinology. 2018;(8):627-636
Abstract
BACKGROUND Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes. METHODS In this multicentre, randomised, double-blind, placebo-controlled, phase 2 study, we randomly assigned (1:1:1:1:1) patients to receive oral placebo or one of four doses of oral dorzagliatin (75 mg once a day, 100 mg once a day, 50 mg twice a day, or 75 mg twice a day) using permuted-block randomisation, with a block size of ten and without stratification. Eligible patients were men or non-fertile women (aged 40-75 years) with type 2 diabetes who had a BMI of 19·0-30·0 kg/m2, were on a diet and exercise regimen, and were previously untreated or treated with metformin or α-glucosidase inhibitor monotherapy. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least one dose of study drug and had both baseline and at least one post-baseline HbA1c value. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02561338. FINDINGS Between Sept 29, 2015, and Aug 17, 2016, we randomly assigned 258 patients to one of the five study groups. At the end of 12 weeks, the least squares mean change in HbA1c from baseline was -0·35% (95% CI -0·60 to -0·10) in the placebo group, -0·39% (-0·64 to -0·14) in the 75 mg once daily group, -0·65% (-0·92 to -0·38) in the 100 mg once daily group, -0·79% (-1·06 to -0·52) in the 50 mg twice daily group, and -1·12% (-1·39 to -0·86) in the 75 mg twice daily group. Compared with the placebo group, the change in HbA1c between baseline and 12 weeks was significant in the 50 mg twice daily (p=0·0104) and the 75 mg twice daily (p<0·0001) groups. The number of adverse events was similar between the treatment groups and the placebo group. There were no reports of drug-related serious adverse events or severe hypoglycaemia. INTERPRETATION Dorzagliatin had a beneficial effect on glycaemic control and was safe and well tolerated over 12 weeks in Chinese patients with type 2 diabetes. FUNDING Hua Medicine, National Major Scientific and Technological Special Project for Significant New Drugs Development, Shanghai Science and Technology Innovation Action Project, Shanghai Pudong District Science and Technology Innovation Action Project, and Shanghai Municipal Commission of Economy and Informatisation Innovation Action Project.