title: Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study (TROICA study).
abstract: To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM).
  
  
  
  We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24.
  
  
  
  The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group.
  
  
  
  Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Eulji General Hospital, Seoul, Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Nam
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
authors.forename: Kyu Jeung
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.
authors.forename: Tae Keun
authors.initials: TK
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Yeungnam University Medical Centre, Daegu, Korea.
authors.forename: Hyoung Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Jaetaek
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea.
authors.forename: Choon Hee
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Byung Joon
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, Seongnam, Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Korea.
authors.forename: Hyeong Kyu
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Daedong General Hospital, Busan, Korea.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.
authors.forename: Kwan Pyo
authors.initials: KP
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.
authors.forename: Chong Hwa
authors.initials: CH
authors.lastname: Kim
authors.affiliation: LG Life Sciences, Seoul, Korea.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010881:Piperidones / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D056910:Republic of Korea / Q000453:epidemiology; D012306:Risk; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010881:Piperidones; D011743:Pyrimidines; D013453:Sulfonylurea Compounds; C534891:LC15-0444; C517652:hemoglobin A1c protein, human
keywords: 
  DPP-4 inhibitor; clinical trial; phase III study