PMID- 35397165
OWN - NLM
STAT- MEDLINE
DCOM- 20220620
LR  - 20220928
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 7
DP  - 2022 Jun 16
TI  - Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and 
      Plasma Metabolites in Type 2 Diabetes.
PG  - 1888-1896
LID - 10.1210/clinem/dgac210 [doi]
AB  - CONTEXT: Cardiovascular benefits of empagliflozin in patients with type 2 
      diabetes mellitus (T2DM) have been reported; however, the underlying mechanism 
      remains unknown. OBJECTIVE: We hypothesized that the cardiovascular benefits of 
      empagliflozin are associated with altered gut microbiota and plasma metabolites, 
      and that empagliflozin may be used as an initial treatment for patients with T2DM 
      at risk of cardiovascular diseases (CVDs). METHODS: This randomized, open-label, 
      3-month, 2-arm clinical trial included 76 treatment-naive patients with T2DM and 
      risk factors for CVD who were treated with either empagliflozin (10 mg/d, n = 40) 
      or metformin (1700 mg/d, n = 36). We investigated changes in clinical parameters 
      related to glucose metabolism and CVD risk factors, gut microbiota using 16S rRNA 
      gene sequencing, and plasma metabolites using LC-MS. RESULTS: We found 
      significant and similar reduction in HbA1c levels and alleviation of glucose 
      metabolism in both groups. However, only empagliflozin improved CVD risk factors. 
      Empagliflozin significantly reshaped the gut microbiota after 1 month of 
      treatment; this alteration was maintained until the end of the trial. 
      Empagliflozin increased the levels of plasma metabolites such as sphingomyelin, 
      but reduced glycochenodeoxycholate, cis-aconitate, and uric acid levels. 
      Concurrently, empagliflozin elevated levels of short-chain fatty acid-producing 
      bacteria such as species from Roseburia, Eubacterium, and Faecalibacterium, and 
      reduced those of several harmful bacteria including Escherichia-Shigella, 
      Bilophila, and Hungatella. CONCLUSION: Empagliflozin may be a superior initial 
      therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may 
      be associated with shifts in gut microbiota and plasma metabolites.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Deng, Xinru
AU  - Deng X
AUID- ORCID: 0000-0003-3747-9310
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Zhang, Chenhong
AU  - Zhang C
AD  - State Key Laboratory of Microbial Metabolism and Ministry of Education Key 
      Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, 
      Shanghai Jiao Tong University, Shanghai 200240, China.
FAU - Wang, Pengxu
AU  - Wang P
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Shi, Xiaoyang
AU  - Shi X
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Wang, Pingping
AU  - Wang P
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Yang, Junpeng
AU  - Yang J
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Wang, Limin
AU  - Wang L
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Tang, Shasha
AU  - Tang S
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Fang, Yuanyuan
AU  - Fang Y
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Liu, Yalei
AU  - Liu Y
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Chen, Yiqi
AU  - Chen Y
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Yuan, Qian
AU  - Yuan Q
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Shang, Jing
AU  - Shang J
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Kan, Quane
AU  - Kan Q
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Yang, Huihui
AU  - Yang H
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Man, Hua
AU  - Man H
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Wang, Danyu
AU  - Wang D
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
FAU - Yuan, Huijuan
AU  - Yuan H
AUID- ORCID: 0000-0002-0486-0994
AD  - Department of Endocrinology, Henan Provincial Key Medicine Laboratory of 
      Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
LA  - eng
GR  - 81970705/National Natural Science Foundation of China/
GR  - 204200510026/Central Plains Thousand Talents Plan/
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 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - HDC1R2M35U (empagliflozin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - J Clin Endocrinol Metab. 2022 Jun 08;:. PMID: 35674101
EIN - J Clin Endocrinol Metab. 2022 Nov 23;107(11):e4330. PMID: 36104307
MH  - Benzhydryl Compounds
MH  - *Cardiovascular Diseases/chemically induced/prevention & control
MH  - *Diabetes Mellitus, Type 2
MH  - *Gastrointestinal Microbiome
MH  - Glucose
MH  - Glucosides
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - RNA, Ribosomal, 16S/genetics
PMC - PMC9202724
OTO - NOTNLM
OT  - cardiovascular disease
OT  - empagliflozin
OT  - gut microbiota
OT  - metabonomics
OT  - type 2 diabetes mellitus
EDAT- 2022/04/10 06:00
MHDA- 2022/06/22 06:00
PMCR- 2022/04/09
CRDT- 2022/04/09 17:04
PHST- 2021/09/29 00:00 [received]
PHST- 2022/04/10 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/04/09 17:04 [entrez]
PHST- 2022/04/09 00:00 [pmc-release]
AID - 6565990 [pii]
AID - dgac210 [pii]
AID - 10.1210/clinem/dgac210 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Jun 16;107(7):1888-1896. doi: 
      10.1210/clinem/dgac210.