ArticleJCI insight2019
SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
140 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Fibroblast growth factor 21 and prognosis of patients with cardiovascular disease: A meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Frontiers in cardiovascular medicine · 2021Pooled it
- The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials.Journal of the American Geriatrics Society · 2025Trial
- Trial
- A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes.Diabetes, obesity & metabolism · 2020 · on this mapTrial
- Bibliometric analysis of SGLT2 inhibitor treatment for diabetic kidney disease.Renal failure · 2026Review
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- Article
- Renal glycosuria triggers a coordinated mannose and glutamine metabolic program to maintain glucose homeostasis.Cell reports · 2026Article
- SGLT2 Inhibitors Promote Diabetic Wound Healing Via AMPK/AKT/mTORC1-Regulated Endothelial Angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Apabetalone Drives a Metabolic Shift Towards Ketogenesis and Reduces Liver Steatosis in Diet-Induced Obesity Mice.Biomedicines · 2026Article
- Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies.Nature reviews. Cardiology · 2026Review
- Sodium-glucose cotransporter 2 inhibitors in breast cancer patients on endocrine therapy: a targeted strategy to mitigate long-term cardiometabolic risk.Journal of translational medicine · 2026Review
- Metabolic Reprogramming Coordinates Mannose and Glutamine Metabolism to Maintain Glucose Homeostasis During Glycosuria.bioRxiv : the preprint server for biology · 2026Article
- Next-generation therapeutics for diabetic kidney disease.Nature reviews. Nephrology · 2026Review
- ChREBP-β Exacerbates Renal Tubular Disorders Caused by Fructose via ATF4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Nutrient-driven histone acetylation underlies energy storage and mobilization.Molecular metabolism · 2026Article
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- The SGLT2 Inhibitor Canagliflozin Promotes β-Cell Regeneration and Restores and Stabilises β-Cell Identity in a Polygenic Model of Severe Early-Onset Type 2 Diabetes.Journal of cellular and molecular medicine · 2026Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Pharmacologic inhibition of the renal sodium/glucose cotransporter-2 induces glycosuria and reduces glycemia. Given that SGLT2 inhibitors (SGLT2i) reduce mortality and cardiovascular risk in type 2 diabetes, improved understanding of molecular mechanisms mediating these metabolic effects is required. Treatment of obese but nondiabetic mice with the SGLT2i canagliflozin (CANA) reduces adiposity, improves glucose tolerance despite reduced plasma insulin, increases plasma ketones, and improves plasma lipid profiles. Utilizing an integrated transcriptomic-metabolomics approach, we demonstrate that CANA modulates key nutrient-sensing pathways, with activation of 5' AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR), independent of insulin or glucagon sensitivity or signaling. Moreover, CANA induces transcriptional reprogramming to activate catabolic pathways, increase fatty acid oxidation, reduce hepatic steatosis and diacylglycerol content, and increase hepatic and plasma levels of FGF21. Given that these phenotypes mirror the effects of FGF21 to promote lipid oxidation, ketogenesis, and reduction in adiposity, we hypothesized that FGF21 is required for CANA action. Using FGF21-null mice, we demonstrate that FGF21 is not required for SGLT2i-mediated induction of lipid oxidation and ketogenesis but is required for reduction in fat mass and activation of lipolysis. Taken together, these data demonstrate that SGLT2 inhibition triggers a fasting-like transcriptional and metabolic paradigm but requires FGF21 for reduction in adiposity.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.