# Beyond Glucose Control: A Comprehensive Review of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Heart Failure, Chronic Kidney Disease, and Nonalcoholic Fatty Liver Disease

**Authors:** Alexander R Sosa, Michael C Sosa

PMC · DOI: 10.7759/cureus.104564 · Cureus · 2026-03-02

## TL;DR

This review explores how SGLT2 inhibitors, originally used for diabetes, also benefit heart failure, kidney disease, and fatty liver disease.

## Contribution

The paper provides a comprehensive synthesis of SGLT2 inhibitors' expanding role beyond glucose control into cardiorenal and metabolic diseases.

## Key findings

- SGLT2 inhibitors reduce heart failure hospitalizations and slow chronic kidney disease progression.
- They show potential benefits in non-alcoholic fatty liver disease.
- Their use is supported by real-world evidence and emerging guidelines.

## Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first introduced to enhance glycemic control in type 2 diabetes mellitus (T2DM). However, a series of large-scale cardiovascular and renal outcomes trials have revealed their substantial benefits in reducing heart failure (HF) hospitalizations, slowing chronic kidney disease (CKD) progression, and improving cardiorenal outcomes, even among non-diabetic populations. Early studies further suggest potential benefits in non-alcoholic fatty liver disease (NAFLD). In this comprehensive review, we synthesize the mechanistic basis, landmark trials, real-world evidence, and emerging guidelines that position SGLT2 inhibitors as cornerstone therapies in the management of HF and CKD, with growing research in NAFLD. By highlighting key clinical outcomes, safety profiles, and cost-effectiveness considerations, we underscore how SGLT2 inhibitors transcend their original role in glucose regulation to provide multifaceted protection across the cardiorenal-metabolic spectrum.

## Linked entities

- **Proteins:** SLC5A2 (solute carrier family 5 member 2)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), heart failure (MONDO:0005252), chronic kidney disease (MONDO:0005300), non-alcoholic fatty liver disease (MONDO:0013209)

## Full-text entities

- **Genes:** FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** hepatic steatosis (MESH:D005234), T2DM (MESH:D003924), adiposity (MESH:D018205), Obesity (MESH:D009765), Kidney Disease (MESH:D007674), HF (MESH:D006333), volume depletion (MESH:C536350), hepatic disease (MESH:D056486), genital mycotic infections (MESH:D015821), DKA (MESH:D016883), metabolic dysfunction (MESH:D008659), hypotension (MESH:D007022), diabetic kidney disease (MESH:D003928), kidney function loss (MESH:D007680), Fournier gangrene (MESH:D018934), HFmrEF (MESH:D054143), HFpEF (MESH:D054144), Liver Disease (MESH:D008107), inflammation (MESH:D007249), albuminuria (MESH:D000419), fibrosing (MESH:D005355), hypertension (MESH:D006973), fracture (MESH:D050723), atherosclerotic (MESH:D050197), genital infection (MESH:D007239), congestion (MESH:D002311), NAFLD (MESH:D065626), cardiovascular death (MESH:D002318), kidney failure (MESH:D051437), Diabetes (MESH:D003920), ESKD (MESH:D007676), liver fibrosis (MESH:D008103), urinary tract infections (MESH:D014552), dizziness (MESH:D004244), CKD (MESH:D051436)
- **Chemicals:** canagliflozin (MESH:D000068896), DAPA (MESH:C020269), empagliflozin (MESH:C570240), alcohol (MESH:D000438), Glucose (MESH:D005947), creatinine (MESH:D003404), ARNI (-), sodium (MESH:D012964), uric acid (MESH:D014527), ketone (MESH:D007659), carbohydrate (MESH:D002241), fatty acid (MESH:D005227), dapagliflozin (MESH:C529054)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12952939/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12952939/full.md

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Source: https://tomesphere.com/paper/PMC12952939