ArticleAmerican journal of physiology. Renal physiology2018
Evaluation of renal and cardiovascular protection mechanisms of SGLT2 inhibitors: model-based analysis of clinical data.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review.ESC heart failure · 2021Pooled it
- Repurposing SGLT2 Inhibitors for Cirrhotic Ascites: From Mechanistic Research to Clinical Exploration.Journal of clinical and translational hepatology · 2026Review
- Cardiac digital twins: a tool to investigate the function and treatment of the diabetic heart.Cardiovascular diabetology · 2025Review
- Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?Journal of veterinary pharmacology and therapeutics · 2025Review
- Hemodynamic Effects of SGLT2 Inhibitors in Patients with and Without Diabetes Mellitus-A Narrative Review.Healthcare (Basel, Switzerland) · 2024Review
- Embracing sex-specific differences in engineered kidney models for enhanced biological understanding of kidney function.Biology of sex differences · 2024Review
- Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat.American journal of physiology. Cell physiology · 2024Article
- SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.Cardiovascular research · 2024Review
- An In Silico Platform to Predict Cardiotoxicity Risk of Anti-tumor Drug Combination with hiPSC-CMs Based In Vitro Study.Pharmaceutical research · 2024Article
- Dapagliflozin ameliorates diabetes-induced spermatogenic dysfunction by modulating the adenosine metabolism along the gut microbiota-testis axis.Scientific reports · 2024Article
- Quantifying the integrated physiological effects of endothelin-1 on cardiovascular and renal function in healthy subjects: a mathematical modeling analysis.Frontiers in pharmacology · 2024Article
- Potential Underlying Mechanisms Explaining the Cardiorenal Benefits of Sodium-Glucose Cotransporter 2 Inhibitors.Advances in therapy · 2024Review
- Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.Circulation · 2023Review
- Understanding the Mechanisms and Treatment of Heart Failure: Quantitative Systems Pharmacology Models with a Focus on SGLT2 Inhibitors and Sex-Specific Differences.Pharmaceutics · 2023Review
- Narrative review investigating the nephroprotective mechanisms of sodium glucose cotransporter type 2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease.Frontiers in endocrinology · 2023Review
- A review of cardiovascular benefits of SGLT2 inhibitors.Medicine · 2022Review
- Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes.Cardiovascular diabetology · 2022Review
- Noncardiac comorbidity clustering in heart failure: an overlooked aspect with potential therapeutic door.Heart failure reviews · 2022Review
- SGLT2 inhibitors in the treatment of type 2 cardiorenal syndrome: Focus on renal tubules.Frontiers in nephrology · 2022Review
- The Potential Roles of Osmotic and Nonosmotic Sodium Handling in Mediating the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Heart Failure.Journal of cardiac failure · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of cardiovascular and renal protection observed in clinical trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are incompletely understood and likely multifactorial, including natriuretic, diuretic, and antihypertensive effects, glomerular pressure reduction, and lowering of plasma and interstitial fluid volume. To quantitatively evaluate the contribution of proposed SGLT2i mechanisms of action on changes in renal hemodynamics and volume status, we coupled a mathematical model of renal function and volume homeostasis with clinical data in healthy subjects administered 10 mg of dapagliflozin once daily. The minimum set of mechanisms necessary to reproduce observed clinical responses (urinary sodium and water excretion, serum creatinine and sodium) was determined, and important unobserved physiological variables (glomerular pressure, blood and interstitial fluid volume) were then simulated. We further simulated the response to SGLT2i in diabetic virtual patients with and without renal impairment. Multiple mechanisms were required to explain the observed response: 1) direct inhibition of sodium and glucose reabsorption through SGLT2, 2) SGLT2-driven inhibition of Na
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