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Cited by 109Diabetes Treatment and ManagementHeart Failure Treatment and ManagementCardiovascular Function and Risk Factors

SGLT2-inhibitors; more than just glycosuria and diuresis

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Fathi, Amir, Vickneson, Keeran, Singh, Jagdeep S.·2021·Heart Failure Reviews
DOI 10.1007/s10741-020-10038-wPMC PMC8024235
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Abstract

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.

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  • Urine glucose determination may also help in the assessment of drug efficacy when using SGLT2 inhibitors, a class of oral anti-diabetic drugs that inhibit glucose reabsorption in the kidney, with elimination of glucose via urine.

    “More recently, urine glucose determination may also help in the assessment of drug efficacy when using sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of oral anti-diabetic drugs that inhibit glucose reabsorption in the kidney, with elimination of glucose via urine 173.”

    From Glucose biosensors in clinical practice: principles, limits and perspectives of currently used devices (2022) · cites this paper as [173]

    The Introduction section “SGLT2 inhibitors – what it says on the tin” (page not provided) says these drugs prevent renal glucose reabsorption, resulting in glucosuria. It does not say that measuring urine glucose helps assess drug efficacy; searches for urine glucose determination and treatment-response monitoring found no such passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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References 111 · Cited by 109

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Authors
Fathi, A., Vickneson, K., & Singh, J. S.
Affiliations
  • National Hospital for Neurology and Neurosurgery (GB)
  • University of Dundee (GB)
Corresponding author
Singh, Jagdeep S.
ORCID
Venue
Heart Failure Reviews
Publisher
Springer Science and Business Media LLC
Published
2020-12-04
Volume
26
Issue
3
Pages
623-642
ISSN
  • 1382-4147 (ISSN-L)
  • 1573-7322
DOI
10.1007/s10741-020-10038-w
PMC
PMC8024235
OpenAlex
W3107243156
Cited by
109
References
111
Citations by year
2026: 12 · 2025: 25 · 2024: 23 · 2023: 27 · 2022: 11 · 2021: 11
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Heart Failure Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion, cc-by)
Funders
  • European Foundation for the Study of Diabetes
  • University of Dundee
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 › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
SGLT2 inhibitors, heart failure, type 2 diabetes, glycosuria, diuresis, mechanism of action, myocardial energetics, calcium balance, renal physiology, cardiovascular risk reduction
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Diuresis, Glycosuria, Humans, Sodium-Glucose Transporter 2

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