PMID- 36657502
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230227
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 188
DP  - 2023 Feb
TI  - Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical 
      evidence to molecular mechanisms.
PG  - 106667
LID - S1043-6618(23)00023-3 [pii]
LID - 10.1016/j.phrs.2023.106667 [doi]
AB  - Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective, well-tolerated, 
      and safe glucose-lowering compounds for patients with type 2 diabetes mellitus 
      (T2DM). SGLT2i benefit encompasses protection from heart and kidney failure, 
      independently of the presence of diabetes. In addition, SGLT2i consistently 
      reduce the risk of hospitalization for heart failure and, although with some 
      heterogeneity between specific members of the class, favourably affect the risk 
      of cardiovascular outcomes. The molecular mechanisms underlying the 
      cardiovascular favourable effect are not fully clarified. Studies testing the 
      efficacy of SGLT2i in human cohorts and experimental models of atherosclerotic 
      cardiovascular disease (ASCVD) have reported significant differences in 
      circulating levels and composition of lipoprotein classes. In randomized clinical 
      trials, small but significant increases in low-density lipoprotein cholesterol 
      (LDL-C) levels have been observed, with a still undefined clinical significance; 
      on the other hand, favourable (although modest) effects on high-density 
      lipoprotein cholesterol (HDL-C) and triglycerides have been reported. At the 
      molecular level, glycosuria may promote a starving-like state that ultimately 
      leads to a metabolic improvement through the mobilization of fatty acids from the 
      adipose tissue and their oxidation for the production of ketone bodies. This, 
      however, may also fuel hepatic cholesterol synthesis, thus inhibiting atherogenic 
      lipoprotein uptake from the liver. Long-term studies collecting detailed 
      information on lipid-lowering therapies at baseline and during the trials with 
      SGLT2i, as well as regularly monitoring lipid profiles are warranted to 
      disentangle the potential implications of SGLT2i in modulating 
      lipoprotein-mediated atherosclerotic cardiovascular risk.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Osto, Elena
AU  - Osto E
AD  - Institute for Clinical Chemistry, University Hospital Zurich and University of 
      Zurich, Zurich, Switzerland; Department of Cardiology, Heart Center, University 
      Hospital Zurich and University of Zurich, Zurich, Switzerland.
FAU - Bonacina, Fabrizia
AU  - Bonacina F
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan, 
      Milan, Italy.
FAU - Pirillo, Angela
AU  - Pirillo A
AD  - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, 
      Milan, Italy.
FAU - Norata, Giuseppe Danilo
AU  - Norata GD
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan, 
      Milan, Italy. Electronic address: danilo.norata@unimi.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230116
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Triglycerides)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Lipoproteins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - *Atherosclerosis/drug therapy
MH  - Triglycerides
MH  - Cholesterol, LDL
MH  - Lipoproteins
MH  - Glucose
MH  - *Cardiovascular Diseases/drug therapy/prevention & control
OTO - NOTNLM
OT  - Atherosclerotic cardiovascular disease
OT  - Lipids
OT  - Low-density lipoprotein cholesterol
OT  - Sodium-glucose cotransporter 2
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/20 06:00
MHDA- 2023/02/15 06:00
CRDT- 2023/01/19 19:22
PHST- 2022/11/17 00:00 [received]
PHST- 2022/12/19 00:00 [revised]
PHST- 2023/01/15 00:00 [accepted]
PHST- 2023/01/20 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/01/19 19:22 [entrez]
AID - S1043-6618(23)00023-3 [pii]
AID - 10.1016/j.phrs.2023.106667 [doi]
PST - ppublish
SO  - Pharmacol Res. 2023 Feb;188:106667. doi: 10.1016/j.phrs.2023.106667. Epub 2023 
      Jan 16.