PMID- 35917580
OWN - NLM
STAT- MEDLINE
DCOM- 20220929
LR  - 20221207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 10
DP  - 2022 Sep 28
TI  - A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin 
      Therapy in Patients with Type 2 Diabetes.
PG  - e4063-e4071
LID - 10.1210/clinem/dgac436 [doi]
AB  - CONTEXT: There is a medical need for effective insulin-independent antidiabetic 
      drugs that can promote pancreatic beta-cell function and have a low risk of 
      hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil 
      (R-Vera), which is able to enhance the survival of beta-cells and has higher 
      cardiovascular safety margin compared with racemic verapamil, was developed as a 
      novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, 
      placebo-controlled clinical trial was designed to evaluate the efficacy and 
      safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients 
      who had inadequate glycemic control on metformin alone. METHODS: Participants 
      were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg 
      per day, or matching placebo, in combination with metformin. The primary endpoint 
      was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A 
      total of 184 eligible participants were randomized to receive either R-Vera or 
      placebo plus metformin. At week 12, significant reductions in HbA1c were observed 
      for R-Vera 300 mg/day (-0.36, P = 0.0373) and 450 mg/day (-0.45, P = 0.0098) 
      compared with placebo. The reduction in HbA1c correlated with decreasing fasting 
      plasma glucose levels and improved HOMA2-beta score. Treatment with R-Vera was well 
      tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: 
      Addition of R-Vera twice daily to ongoing metformin therapy significantly 
      improved glycemic control in T2DM patients. The favorable efficacy and safety 
      profile of R-Vera 300 mg/day can be considered as the appropriate dose for 
      clinical practice.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Wang, Chih-Yuan
AU  - Wang CY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      National Taiwan University Hospital, Taipei 100229, Taiwan.
FAU - Huang, Kuo-Chin
AU  - Huang KC
AD  - Department of Family Medicine, National Taiwan University Hospital, Taipei 
      100229, Taiwan.
FAU - Lu, Chia-Wen
AU  - Lu CW
AD  - Department of Family Medicine, National Taiwan University Hospital, Taipei 
      100229, Taiwan.
FAU - Chu, Chih-Hsun
AU  - Chu CH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan.
FAU - Huang, Chien-Ning
AU  - Huang CN
AD  - Institute of Medicine, Chung Shan Medical University & Hospital, Taichung 402306, 
      Taiwan.
FAU - Chen, Harn-Shen
AU  - Chen HS
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans 
      General Hospital, Taipei 112201, Taiwan.
FAU - Lee, I-Te
AU  - Lee IT
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Taichung Veterans General Hospital, Taichung 407219, Taiwan.
FAU - Chen, Jung-Fu
AU  - Chen JF
AD  - Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung 
      Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 
      833401, Taiwan.
FAU - Chen, Ching-Chu
AU  - Chen CC
AD  - Division of Endocrinology and Metabolism, Department of Medicine, China Medical 
      University Hospital, Taichung 404332, Taiwan.
FAU - Chen, Chung-Sen
AU  - Chen CS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei 
      City Hospital Zhongxiao Branch, Taipei 115006, Taiwan.
FAU - Hsieh, Chang-Hsun
AU  - Hsieh CH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Tri-Service General Hospital, Taipei 114202, Taiwan.
FAU - Tien, Kai-Jen
AU  - Tien KJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi 
      Mei Medical Center, Tainan 710402, Taiwan.
FAU - Chien, Hung-Yu
AU  - Chien HY
AD  - Department of Endocrinology and Metabolism, Taipei City Hospital Renai Branch, 
      Taipei 106243, Taiwan.
FAU - Huang, Yu-Yao
AU  - Huang YY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang 
      Gung Memorial Hospital, Taoyuan 333423, Taiwan.
FAU - Hsu, Jui-Pao
AU  - Hsu JP
AD  - Center Laboratories Inc., Taipei 115603, Taiwan.
FAU - Shane, Guang-Tzuu
AU  - Shane GT
AD  - Center Laboratories Inc., Taipei 115603, Taiwan.
FAU - Chang, Ai-Ching
AU  - Chang AC
AD  - Lumosa Therapeutics Co., Ltd., Taipei 115603, Taiwan.
FAU - Wu, Yen-Chieh
AU  - Wu YC
AUID- ORCID: 0000-0002-9143-6533
AD  - Lumosa Therapeutics Co., Ltd., Taipei 115603, Taiwan.
FAU - Sheu, Wayne Huey-Herng
AU  - Sheu WH
AUID- ORCID: 0000-0002-8805-8340
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans 
      General Hospital, Taipei 112201, Taiwan.
AD  - Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, 
      Taiwan.
LA  - eng
SI  - ClinicalTrials.gov/NCT03317028
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
RN  - CJ0O37KU29 (Verapamil)
SB  - IM
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - *Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/adverse effects
MH  - Insulin/therapeutic use
MH  - *Metformin
MH  - Treatment Outcome
MH  - Verapamil/therapeutic use
PMC - PMC9516171
OTO - NOTNLM
OT  - HbA1c
OT  - R-form verapamil
OT  - antidiabetic drug
OT  - metformin
OT  - type 2 diabetes
EDAT- 2022/08/03 06:00
MHDA- 2022/09/30 06:00
PMCR- 2022/08/02
CRDT- 2022/08/02 17:23
PHST- 2021/12/30 00:00 [received]
PHST- 2022/08/03 06:00 [pubmed]
PHST- 2022/09/30 06:00 [medline]
PHST- 2022/08/02 17:23 [entrez]
PHST- 2022/08/02 00:00 [pmc-release]
AID - 6653488 [pii]
AID - dgac436 [pii]
AID - 10.1210/clinem/dgac436 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4063-e4071. doi: 
      10.1210/clinem/dgac436.