Sodium-glucose cotransporter 2 inhibition: cardioprotection by treating diabetes—a translational viewpoint explaining its potential salutary effects
Open accessAbstract
Diabetes is a growing epidemic worldwide characterized by an elevated concentration of blood glucose, associated with a high incidence of cardiovascular disease and mortality. Although in general reduction of hyperglycaemia is considered a therapeutic goal, hypoglycaemic therapies do not necessarily reduce cardiovascular mortality and may even aggravate cardiovascular risk factors, such as body weight. A new class of antidiabetic drugs acts by inhibition of the sodium-glucose cotransporter 2 (SGLT2), which (partially) prevents reabsorption of glucose from the renal filtrate. The induction of glucose excretion via the urine (glycosuria) was turned into an effective strategy to reduce blood glucose. Ancillary advantages are the caloric and volumetric loss and thereby the reduction of body weight and blood pressure. Additionally, SGLT2 inhibition has been suggested to exert direct cardioprotective effects by the reduction of cardiac fibrosis, inflammation, and oxidative stress. This article summarizes the functional consequences of SGLT2 inhibition on the diabetic and hyperglycaemic organism. We especially focused on the effects on the kidney and the cardiovascular system as described in experimental studies. The interesting observations in experimental studies may extend to clinical medicine, as a recent trial reported a decrease in heart failure outcomes in patients at high cardiovascular risk. In conclusion, SGLT2 inhibition represents a novel treatment, which might be a promising target not only to (further) reduce blood glucose but also to target other cardiovascular risk factors. More research and long-term follow-ups will reveal the specific influence of SGLT2 inhibition on the circulatory system and cardiovascular outcomes.
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Effects on the cardiometabolic profile may be effective in HFpEF.
“So, these findings validated the concept that effects on the cardiometabolic profile may be effective in HFpEF.12,13”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [13]
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Flagged first, then by citations
Research works printed but not linked: 1
- Porte D Jr. Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications. Dia- betes Metab Res Rev 2001;17:181 -188.
Cited by
Sorted by citations
Withaar, C., Meems, L. M. G., Markousis-Mavrogenis, G., Boogerd, C. J., Silljé, H. H. W., Schouten, E. M., Dokter, M. M., Voors, A. A., Westenbrink, B. D., Lam, C. S. P., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa256 · Cited by 223 · see citing works
The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF
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Self-citation
- Authors
- de Leeuw, A. E., & de Boer, R. A.
- Venue
- European Heart Journal - Cardiovascular Pharmacotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04-18
- Volume
- 2
- Issue
- 4
- Pages
- 244-255
- ISSN
- 2055-6837 (ISSN-L)
- 2055-6845
- OpenAlex
- W2345496704
- Cited by
- 46
- References
- 135
- Citations by year
- 2025: 2 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 10 · 2017: 5 · 2016: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- European Heart Journal - Cardiovascular Pharmacotherapy (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Netherlands Organization for Scientific Research (917.13.350)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- SGLT2 inhibition, SGLT2, diabetes mellitus, cardioprotection, heart failure, glycosuria, renal glucose reabsorption, cardiovascular risk, weight loss, blood pressure reduction, myocardial fibrosis, oxidative stress, inflammation, antidiabetic drugs
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Blood Glucose, Cardiotonic Agents, Diabetes Mellitus, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Sodium-Glucose Transporter 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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