title: Efficacy and safety of linagliptin/metformin single-pill combination as initial therapy in drug-naïve Asian patients with type 2 diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, 100853 Beijing, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, 100853 Beijing, China. Electronic address: panchy301@126.com.
authors.forename: Changyu
authors.initials: C
authors.lastname: Pan
authors.affiliation: Boehringer Ingelheim International Trading Co., Ltd., 29/F, Park Place, 1601 Nanjing Road (West), Shanghai 200040, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Fan
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hehnke
authors.affiliation: Tong Ji Hospital of Tongji University, No. 1239, SiPing Road, Shanghai, China. Electronic address: 13621688858@163.com.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Sichuan Provincial People's Hospital, 32 W 2nd Section, First Ring Road, Qingyang, Chengdu, Sichuan, China. Electronic address: zxj9819@163.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Yueyang First People's Hospital, 3 Yunzhong W Road, Yunxi, Yueyang, Hunan, China. Electronic address: 2050wxy@sina.cn.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jiangxi Provincial People's Hospital, 2 Aiguo Road, Donghu, Nanchang, Jiangxi, China. Electronic address: easd04ljd@126.com.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Liwan, Guangzhou, Guangdong, China. Electronic address: zhangying30412@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Xigang, Dalian, Liaoning, China. Electronic address: Dujianling63@163.com.
authors.forename: Jianling
authors.initials: J
authors.lastname: Du
authors.affiliation: Nanjing First Hospital, 300 Guangzhou Road, Nanjing, Jiangsu, China. Electronic address: majianhua@china.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ma
authors.affiliation: Boehringer Ingelheim International Trading Co., Ltd., 29/F, Park Place, 1601 Nanjing Road (West), Shanghai 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000208:ethnology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D013607:Tablets; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; D013607:Tablets
keywords: Asian population; Combination therapy; Linagliptin; Metformin; Type 2 diabetes