PMID- 33769656
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 23
IP  - 8
DP  - 2021 Aug
TI  - Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes 
      inadequately controlled with metformin: A multicentre, randomized, double-blind, 
      placebo-controlled, phase 3 trial.
PG  - 1754-1764
LID - 10.1111/dom.14389 [doi]
AB  - AIM: To evaluate the efficacy and safety of henagliflozin in patients with type 2 
      diabetes mellitus (T2DM) inadequately controlled with metformin. MATERIAL AND 
      METHODS: This multicentre phase 3 trial included a 24-week randomized, 
      double-blind, placebo-controlled period, followed by a 28-week extension period. 
      Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% 
      (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), 
      henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, 
      patients on placebo were switched to 5 mg or 10 mg henagliflozin for the 
      additional 28-week treatment, and patients on henagliflozin during 24-week 
      treatment period maintained this initial therapy. The primary endpoint was change 
      in HbA1c from baseline to Week 24. RESULTS: At Week 24, the least squares mean 
      HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) 
      and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all 
      P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered 
      fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood 
      pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 
      mmol/mol) at Week 24. The trends in these improvements were sustained over an 
      additional 28 weeks. Slightly higher proportions of ketosis and presence of urine 
      ketone bodies were observed in patients treated with henagliflozin compared to 
      placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia 
      were reported. CONCLUSIONS: Henagliflozin 5 mg or 10 mg as add-on therapy to 
      metformin provided a new therapeutic option for the treatment of T2DM patients 
      who have inadequate glycaemic control with metformin alone, and was generally 
      well tolerated.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Weng, Jianping
AU  - Weng J
AUID- ORCID: 0000-0002-7889-1697
AD  - Department of Endocrinology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      Anhui, China.
FAU - Zeng, Longyi
AU  - Zeng L
AD  - Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Zhang, Yuwei
AU  - Zhang Y
AD  - Huaxi Hospital of Sichuan University, Chengdu, China.
FAU - Qu, Shen
AU  - Qu S
AD  - Shanghai 10th People's Hospital, Shanghai, China.
FAU - Wang, Xueying
AU  - Wang X
AD  - Jinzhou Central Hospital, Jinzhou, China.
FAU - Li, Ping
AU  - Li P
AD  - Yuncheng Central Hospital, Taiyuan, China.
FAU - Fu, Liujun
AU  - Fu L
AD  - First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 
      China.
FAU - Ma, Boqing
AU  - Ma B
AD  - Hebei General Hospital, Shijiazhuang, China.
FAU - Ye, Shandong
AU  - Ye S
AD  - Department of Endocrinology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      Anhui, China.
FAU - Sun, Jiao
AU  - Sun J
AD  - Huadong Hospital Affiliated to Fudan University, Shanghai, China.
FAU - Lu, Weiping
AU  - Lu W
AD  - First Affiliated Huai'an Hospital of Nanjing Medical University, Huai'an, China.
FAU - Liu, Zhiwen
AU  - Liu Z
AD  - Shanghai Xuhui District Central Hospital, Shanghai, China.
FAU - Chen, Daoxiong
AU  - Chen D
AD  - Hainan General Hospital, Haikou, China.
FAU - Cheng, Zhifeng
AU  - Cheng Z
AD  - Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Liu, Haiyan
AU  - Liu H
AD  - Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.
FAU - Zhang, Tao
AU  - Zhang T
AD  - Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.
FAU - Zou, Jianjun
AU  - Zou J
AD  - Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.
LA  - eng
GR  - This study was funded by Jiangsu Hengrui Medicine./
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210414
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 21P2M98388 (henagliflozin)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Blood Glucose
MH  - Bridged Bicyclo Compounds, Heterocyclic
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - *Metformin/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - add-on therapy
OT  - henagliflozin
OT  - metformin
OT  - sodium-glucose cotransporter type-2 inhibitor
OT  - type 2 diabetes mellitus
EDAT- 2021/03/27 06:00
MHDA- 2021/08/07 06:00
CRDT- 2021/03/26 13:06
PHST- 2021/03/01 00:00 [revised]
PHST- 2020/12/23 00:00 [received]
PHST- 2021/03/19 00:00 [accepted]
PHST- 2021/03/27 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2021/03/26 13:06 [entrez]
AID - 10.1111/dom.14389 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2021 Aug;23(8):1754-1764. doi: 10.1111/dom.14389. Epub 2021 
      Apr 14.