PMID- 35581902
OWN - NLM
STAT- MEDLINE
DCOM- 20220803
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 24
IP  - 9
DP  - 2022 Sep
TI  - A double-blind, Randomized controlled trial on glucose-lowering EFfects and 
      safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with 
      INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: 
      REFIND study.
PG  - 1800-1809
LID - 10.1111/dom.14766 [doi]
AB  - AIMS: To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 
      mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 
      diabetes mellitus (T2DM) with inadequate glucose control on metformin and 
      dipeptidyl peptidase (DPP4) inhibitor therapy. MATERIALS AND METHODS: In this 
      phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, 
      patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor 
      combination therapy were randomized to receive either low-dose or standard-dose 
      lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone 
      in terms of glycaemic control, expressed as the difference in mean glycated 
      haemoglobin levels at week 24 relative to baseline values and compared with 
      standard-dose lobeglitazone, using 0.5% non-inferiority margin. RESULTS: At week 
      24, the mean glycated haemoglobin levels were 6.87 +/- 0.54% and 6.68 +/- 0.46% in 
      low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The 
      between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing 
      non-inferiority of the low-dose lobeglitazone. Mean body weight changes were 
      significantly greater in the standard-dose group (1.36 +/- 2.23 kg) than in the 
      low-dose group (0.50 +/- 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile 
      and liver enzyme levels showed no significant difference between the groups. 
      Overall treatment-emergent adverse events (including weight gain, oedema and 
      hypoglycaemia) occurred more frequently in the standard-dose group. CONCLUSIONS: 
      Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination 
      resulted in a non-inferior glucose-lowering outcome and fewer adverse events 
      compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone 
      might be one option for individualized strategy in patients with T2DM.
CI  - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Ryang, Soree
AU  - Ryang S
AUID- ORCID: 0000-0002-5251-5554
AD  - Department of Internal Medicine, Pusan National University Hospital, Pusan 
      National University School of Medicine, Busan, South Korea.
AD  - Biomedical Research Institute, Pusan National University Hospital, Busan, South 
      Korea.
FAU - Kim, Sang Soo
AU  - Kim SS
AUID- ORCID: 0000-0002-9687-8357
AD  - Department of Internal Medicine, Pusan National University Hospital, Pusan 
      National University School of Medicine, Busan, South Korea.
AD  - Biomedical Research Institute, Pusan National University Hospital, Busan, South 
      Korea.
FAU - Bae, Ji Cheol
AU  - Bae JC
AUID- ORCID: 0000-0002-4763-5797
AD  - Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan 
      University School of Medicine, Changwon, South Korea.
FAU - Han, Ji Min
AU  - Han JM
AUID- ORCID: 0000-0002-7881-9732
AD  - Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan 
      University School of Medicine, Changwon, South Korea.
FAU - Kwon, Su Kyoung
AU  - Kwon SK
AD  - Department of Internal Medicine, Kosin University Gospel Hospital, Kosin 
      University College of Medicine, Busan, South Korea.
FAU - Kim, Young Il
AU  - Kim YI
AUID- ORCID: 0000-0002-2960-1040
AD  - Department of Internal Medicine, Ulsan University Hospital, University of Ulsan 
      College of Medicine, Ulsan, South Korea.
FAU - Nam-Goong, Il Seong
AU  - Nam-Goong IS
AUID- ORCID: 0000-0002-0492-0467
AD  - Department of Internal Medicine, Ulsan University Hospital, University of Ulsan 
      College of Medicine, Ulsan, South Korea.
FAU - Kim, Eun Sook
AU  - Kim ES
AUID- ORCID: 0000-0002-9311-4642
AD  - Department of Internal Medicine, Ulsan University Hospital, University of Ulsan 
      College of Medicine, Ulsan, South Korea.
FAU - Kim, Mi-Kyung
AU  - Kim MK
AUID- ORCID: 0000-0003-1111-9122
AD  - Department of Internal Medicine, Inje University Haeundae Paik Hospital, College 
      of Medicine, Inje University, Busan, South Korea.
FAU - Lee, Chang Won
AU  - Lee CW
AUID- ORCID: 0000-0002-6184-7171
AD  - Department of Internal Medicine, Busan St. Mary's Hospital, Busan, South Korea.
FAU - Yoo, Soyeon
AU  - Yoo S
AD  - Department of Internal Medicine, Jeju National University Hospital, Jeju National 
      University School of Medicine, Jeju, South Korea.
FAU - Koh, Gwanpyo
AU  - Koh G
AUID- ORCID: 0000-0002-6020-2777
AD  - Department of Internal Medicine, Jeju National University Hospital, Jeju National 
      University School of Medicine, Jeju, South Korea.
FAU - Kwon, Min Jeong
AU  - Kwon MJ
AUID- ORCID: 0000-0002-9616-870X
AD  - Division of Endocrinology & Metabolism, Department of Internal Medicine, Busan 
      Paik Hospital, College of Medicine, Inje University, Busan, South Korea.
FAU - Park, Jeong Hyun
AU  - Park JH
AUID- ORCID: 0000-0002-0045-4438
AD  - Division of Endocrinology & Metabolism, Department of Internal Medicine, Busan 
      Paik Hospital, College of Medicine, Inje University, Busan, South Korea.
FAU - Kim, In Joo
AU  - Kim IJ
AUID- ORCID: 0000-0003-1765-0774
AD  - Department of Internal Medicine, Pusan National University Hospital, Pusan 
      National University School of Medicine, Busan, South Korea.
AD  - Biomedical Research Institute, Pusan National University Hospital, Busan, South 
      Korea.
LA  - eng
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220609
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazolidinediones)
RN  - 9100L32L2N (Metformin)
RN  - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases)
RN  - IY9XDZ35W2 (Glucose)
RN  - MY89F08K5D (lobeglitazone)
SB  - IM
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2/chemically induced/drug therapy
MH  - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects
MH  - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Glucose/therapeutic use
MH  - Glycated Hemoglobin
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - *Metformin/therapeutic use
MH  - Protease Inhibitors/therapeutic use
MH  - Pyrimidines
MH  - Thiazolidinediones
MH  - Treatment Outcome
PMC - PMC9541308
OTO - NOTNLM
OT  - antidiabetic drugs
OT  - beta-cell function
OT  - glycaemic control
OT  - thiazolidinediones
OT  - type 2 diabetes
COIS- This study was supported by a research grant from Chong Kun Dang Pharmaceutical 
      Corporation, Seoul, Republic of Korea. The authors declare that they have no 
      competing interests.
EDAT- 2022/05/19 06:00
MHDA- 2022/08/04 06:00
PMCR- 2022/10/07
CRDT- 2022/05/18 01:22
PHST- 2022/04/06 00:00 [revised]
PHST- 2022/02/23 00:00 [received]
PHST- 2022/04/18 00:00 [accepted]
PHST- 2022/05/19 06:00 [pubmed]
PHST- 2022/08/04 06:00 [medline]
PHST- 2022/05/18 01:22 [entrez]
PHST- 2022/10/07 00:00 [pmc-release]
AID - DOM14766 [pii]
AID - 10.1111/dom.14766 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2022 Sep;24(9):1800-1809. doi: 10.1111/dom.14766. Epub 2022 
      Jun 9.