Yiming Mu1, Changyu Pan2, Bei Fan3, Uwe Hehnke4, Xiuzhen Zhang5, Xuejun Zhang6, Xiaoyue Wang7, Jingdong Liu8, Ying Zhang9, Jianling Du10, Jianhua Ma11, Yan Gong3. 1. Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, 100853 Beijing, China. 2. Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, 100853 Beijing, China. Electronic address: panchy301@126.com. 3. Boehringer Ingelheim International Trading Co., Ltd., 29/F, Park Place, 1601 Nanjing Road (West), Shanghai 200040, China. 4. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim, Germany. 5. Tong Ji Hospital of Tongji University, No. 1239, SiPing Road, Shanghai, China. Electronic address: 13621688858@163.com. 6. Sichuan Provincial People's Hospital, 32 W 2nd Section, First Ring Road, Qingyang, Chengdu, Sichuan, China. Electronic address: zxj9819@163.com. 7. Yueyang First People's Hospital, 3 Yunzhong W Road, Yunxi, Yueyang, Hunan, China. Electronic address: 2050wxy@sina.cn. 8. Jiangxi Provincial People's Hospital, 2 Aiguo Road, Donghu, Nanchang, Jiangxi, China. Electronic address: easd04ljd@126.com. 9. The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan, Guangzhou, Guangdong, China. Electronic address: zhangying30412@163.com. 10. The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Xigang, Dalian, Liaoning, China. Electronic address: Dujianling63@163.com. 11. Nanjing First Hospital, 300 Guangzhou Road, Nanjing, Jiangsu, China. Electronic address: majianhua@china.com.
Abstract
AIM: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control. METHODS:Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2.5mg/metformin 500mg bid; or linagliptin 2.5mg/metformin 1000mg bid. Patients with severe hyperglycemia (HbA1c ⩾11.0% [97mmol/mol]) received linagliptin 2.5mg/metformin 1000mg bid or linagliptin 5mg qd (switched at week 12 from linagliptin to SPC if HbA1c >8.0% [64mmol/mol]). The main group primary endpoint was HbA1c change from baseline to week 24. RESULTS: At week 24, adjusted mean change from baseline in HbA1c (main group, n=733) was: linagliptin 5mg qd, -1.3%; metformin 500mg bid, -1.6%; metformin 1000mg bid, -2.1%; linagliptin 2.5mg/metformin 500mg bid, -2.2%; linagliptin 2.5mg/metformin 1000mg bid, -2.3%. The first test of primary HbA1c analysis (linagliptin 2.5mg/metformin 1000mg bid vs. metformin 1000mg bid) was borderline non-significant; however, SPCs produced significantly greater reductions in HbA1c from baseline versus respective monotherapies in all but one pre-defined sensitivity analysis. In the severe hyperglycemia group (n=143), linagliptin 2.5mg/metformin 1000mg bid produced a superior HbA1c reduction (-4.7%) versus linagliptin 5mg qd (-3.5%) after 12weeks. Hypoglycemic adverse events were low across groups. CONCLUSIONS:Initial linagliptin/metformin SPC significantly improved glycemic control in this population.
RCT Entities:
AIM: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control. METHODS:Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2.5mg/metformin 500mg bid; or linagliptin 2.5mg/metformin 1000mg bid. Patients with severe hyperglycemia (HbA1c ⩾11.0% [97mmol/mol]) received linagliptin 2.5mg/metformin 1000mg bid or linagliptin 5mg qd (switched at week 12 from linagliptin to SPC if HbA1c >8.0% [64mmol/mol]). The main group primary endpoint was HbA1c change from baseline to week 24. RESULTS: At week 24, adjusted mean change from baseline in HbA1c (main group, n=733) was: linagliptin 5mg qd, -1.3%; metformin 500mg bid, -1.6%; metformin 1000mg bid, -2.1%; linagliptin 2.5mg/metformin 500mg bid, -2.2%; linagliptin 2.5mg/metformin 1000mg bid, -2.3%. The first test of primary HbA1c analysis (linagliptin 2.5mg/metformin 1000mg bid vs. metformin 1000mg bid) was borderline non-significant; however, SPCs produced significantly greater reductions in HbA1c from baseline versus respective monotherapies in all but one pre-defined sensitivity analysis. In the severe hyperglycemia group (n=143), linagliptin 2.5mg/metformin 1000mg bid produced a superior HbA1c reduction (-4.7%) versus linagliptin 5mg qd (-3.5%) after 12weeks. Hypoglycemic adverse events were low across groups. CONCLUSIONS: Initial linagliptin/metforminSPC significantly improved glycemic control in this population.
Authors: Linong Ji; Juliana C N Chan; Miao Yu; Kun Ho Yoon; Sin Gon Kim; Sung Hee Choi; Chien-Ning Huang; Shih Te Tu; Chih-Yuan Wang; Päivi Maria Paldánius; Wayne H H Sheu Journal: Diabetes Obes Metab Date: 2020-11-09 Impact factor: 6.577