Evidence mapPaperPMID 41479267Full record

ReviewEndocrinology and metabolism (Seoul, Korea)2025

SGLT2 Inhibitors as Systemic Metabolic Modulators: Linking Glucose Excretion to Liver Function Restoration.

Seung Wan Noh, Han Sol Ryu, Yong-Ho Kim, Byung-Chul Oh

Abstract readReview
In one paragraph

Review in Endocrinology and metabolism (Seoul, Korea), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Observational
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Seung Wan NohDepartment of Health Science and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon University, Incheon, Korea.
Han Sol RyuDepartment of Health Science and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon University, Incheon, Korea.
Yong-Ho KimDepartment of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Korea.
Byung-Chul OhDepartment of Health Science and Technology, Gachon Advanced Institute for Health Science and Technology, Gachon University, Incheon, Korea.

Funding

Gachon University GCU-202406080001Ministry of Science and ICTNational Research Foundation of Korea 2021R1A5A2030333National Research Foundation of Korea 2022R1A2C2092700
6 · The paper itself

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as paradigm-shifting therapeutics that extend beyond glycemic regulation, to conferring profound hepatometabolic benefits. This review delineates the multifaceted mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD), with an emphasis on systemic metabolic remodeling, mitochondrial protection, and intracellular calcium restoration. By promoting glucosuria-induced energy depletion, SGLT2 inhibition alleviates insulin resistance, suppresses hepatic lipogenesis, and activates adenosine monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α pathways that reprogram hepatocellular metabolism toward achieving lipid oxidation and autophagy. Mechanistically, SGLT2 inhibitors restore intracellular Ca2+ homeostasis via sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) activation, mitigating endoplasmic reticulum (ER) stress and normalizing Ca2+-phosphoinositide (PIP)-protein kinase B (AKT) signaling, collectively reinforcing insulin responsiveness and ER-mitochondrial crosstalk. Clinically, these effects translate into consistently reducing hepatic fat, aminotransferases, and fibrosis markers in both diabetic and nondiabetic patients with MASLD. Furthermore, SGLT2 inhibitors uniquely integrate renal energy regulation with hepatic resilience through the Ca2+-PIP-SERCA axis, positioning them as prototype systemic modulators of metabolic homeostasis. Future translational efforts should refine patient stratification using metabolomic and Ca2+-imaging biomarkers to delineate therapeutic responders and advance next-generation SGLT2 analogs targeting Ca2+-dependent metabolic signaling. Collectively, SGLT2 inhibitors represent a new metabolic therapeutic class that unify glucose, lipid, and Ca2+ regulation to restore hepatocellular functions in metabolic liver diseases.

Indexed as

Fatty LiverGlucoseLiverMetabolic DiseasesSodium-Glucose Transporter 2 InhibitorsAnimalsEndoplasmic ReticulumHumansInsulin ResistanceLipogenesisSignal TransductionGlucoseSodium-Glucose Transporter 2 InhibitorsEndoplasmic reticulum stressInsulin resistanceIntracellular calcium homeostasisLiver diseasesSarcoplasmic reticulum calcium-transporting ATPasesSodium-glucose transporter 2 inhibitors

Identifiers

PMID41479267
PMCPMC12765894

What Socratic holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.