Efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes: A double-blind randomized controlled trial (INICOM study).
Gemigliptin is a new dipeptidyl peptidase-IV inhibitor. We investigated the efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes (T2D).



A total of 433 T2D patients with a glycosylated haemoglobin (HbA1c) level of 7.5% to 11.0% and a fasting plasma glucose (FPG) concentration <270 mg/dL were randomly assigned to 3 groups: (1) gemigliptin 50 mg qd + metformin 1000 to 2000 mg qd (titrated individually), (2) gemigliptin 50 mg qd, or (3) metformin 1000 to 2000 mg qd. The primary end-point was the change in HbA1c level after 24 weeks. Secondary end-points were the changes in FPG, insulin, proinsulin and C-peptide levels. The percentages of responders who achieved an HbA1c level <7% (or <6.5%) were compared between treatment groups.



Baseline HbA1c levels were 8.7% in all groups. The mean changes in HbA1c level from baseline to week 24 were -2.06%, -1.24% and -1.47% in the combination, gemigliptin monotherapy and metformin monotherapy groups, respectively. The 95% confidence intervals for between-group differences in HbA1c changes were -1.02 to -0.63 in the combination group vs the gemigliptin group and -0.82 to -0.41 vs the metformin group, which confirmed the superiority of combination therapy. A significantly higher percentage of patients in the combination therapy group reached the target HbA1c level <7% (or <6.5%) compared with the monotherapy groups. No severe side effects were observed.



In T2D patients, the initial combination of gemigliptin and metformin had superior efficacy without safety concerns compared with monotherapy with either drug.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Soo
S
Lim
Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea.
Kyung Ah
KA
Han
Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
JaeMyung
J
Yu
Cardio-Metabolic Research Group, Department of Social Medicine, Sanpasitthiprasong Hospital, Ubon Ratchathani, Thailand.
Parinya
P
Chamnan
Department of Endocrinology and Metabolism, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, Korea.
Eun Sook
ES
Kim
Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Kun-Ho
KH
Yoon
Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
Sam
S
Kwon
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Min Kyong
MK
Moon
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea.
Kwan Woo
KW
Lee
Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
Dong-Jun
DJ
Kim
Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
Mikyung
M
Kim
Nan Hospital, Nan, Thailand.
Manaj
M
Wongtanate
LG Life Sciences, Seoul, Korea.
Eun Young
EY
Kim
LG Life Sciences, Seoul, Korea.
Sung-Ho
SH
Kim
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Moon-Kyu
MK
Lee
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010881:Piperidones / Q000627:therapeutic use*; D011384:Proinsulin / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D056910:Republic of Korea; D013785:Thailand; D016896:Treatment Outcome
D001786:Blood Glucose; D002096:C-Peptide; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010881:Piperidones; D011384:Proinsulin; D011743:Pyrimidines; C534891:LC15-0444; C517652:hemoglobin A1c protein, human

DPP-IV inhibitor; phase III study; type 2 diabetes