PMID- 33274396
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20240331
IS  - 1573-7322 (Electronic)
IS  - 1382-4147 (Print)
IS  - 1382-4147 (Linking)
VI  - 26
IP  - 3
DP  - 2021 May
TI  - SGLT2-inhibitors; more than just glycosuria and diuresis.
PG  - 623-642
LID - 10.1007/s10741-020-10038-w [doi]
AB  - Heart failure (HF) continues to be a serious public health challenge despite 
      significant advancements in therapeutics and is often complicated by multiple 
      other comorbidities. Of particular concern is type 2 diabetes mellitus (T2DM) 
      which not only amplifies the risk, but also limits the treatment options 
      available to patients. The sodium-glucose linked cotransporter subtype 2 
      (SGLT2)-inhibitor class, which was initially developed as a treatment for T2DM, 
      has shown great promise in reducing cardiovascular risk, particularly around HF 
      outcomes - regardless of diabetes status.There are ongoing efforts to elucidate 
      the true mechanism of action of this novel drug class. Its primary mechanism of 
      inducing glycosuria and diuresis from receptor blockade in the renal nephron 
      seems unlikely to be responsible for the rapid and striking benefits seen in 
      clinical trials. Early mechanistic work around conventional therapeutic targets 
      seem to be inconclusive. There are some emerging theories around its effect on 
      myocardial energetics and calcium balance as well as on renal physiology. In this 
      review, we discuss some of the cutting-edge hypotheses and concepts currently 
      being explored around this drug class in an attempt better understand the 
      molecular mechanics of this novel agent.
FAU - Fathi, Amir
AU  - Fathi A
AUID- ORCID: 0000-0002-7517-2566
AD  - Department of Neuroanaesthesia and Critical Care, National Hospital for Neurology 
      and Neurosurgery, University College London, London, UK.
FAU - Vickneson, Keeran
AU  - Vickneson K
AUID- ORCID: 0000-0002-2413-4770
AD  - Division of Molecular and Clinical Medicine, School of Medicine, University of 
      Dundee, Dundee, UK.
FAU - Singh, Jagdeep S
AU  - Singh JS
AUID- ORCID: 0000-0002-7358-9712
AD  - Division of Molecular and Clinical Medicine, School of Medicine, University of 
      Dundee, Dundee, UK. jxsingh@dundee.ac.uk.
AD  - Department of Cardiology, The Edinburgh Heart Center, Royal Infirmary of 
      Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK. 
      jxsingh@dundee.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20201204
PL  - United States
TA  - Heart Fail Rev
JT  - Heart failure reviews
JID - 9612481
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Diuresis
MH  - *Glycosuria
MH  - Humans
MH  - Sodium-Glucose Transporter 2
MH  - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
PMC - PMC8024235
OTO - NOTNLM
OT  - Calcium handling
OT  - Heart failure
OT  - Myocardial energetics
OT  - Renal disease
OT  - SGLT2-inhibitors
OT  - Ventricular remodelling
COIS- JSS has received financial and non-financial support from Boehringer Ingelheim, 
      Astra Zeneca and Merck Sharp and Dohme for work that is relevant but unrelated to 
      this article. AF and KV report no conflict of interest.
EDAT- 2020/12/05 06:00
MHDA- 2021/12/15 06:00
PMCR- 2020/12/04
CRDT- 2020/12/04 05:49
PHST- 2020/10/05 00:00 [accepted]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/12/04 05:49 [entrez]
PHST- 2020/12/04 00:00 [pmc-release]
AID - 10.1007/s10741-020-10038-w [pii]
AID - 10038 [pii]
AID - 10.1007/s10741-020-10038-w [doi]
PST - ppublish
SO  - Heart Fail Rev. 2021 May;26(3):623-642. doi: 10.1007/s10741-020-10038-w. Epub 
      2020 Dec 4.