ArticleCellular and molecular life sciences : CMLS2022
Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 5 of them syntheses that pooled it.
What it found
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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
79 citing papers in PubMed, 5 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: a systematic review based on COVID-19.Endocrine · 2024Pooled it
- The link between hyperuricemia and diabetes: insights from a quantitative analysis of scientific literature.Frontiers in endocrinology · 2024Pooled it
- The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials.BMC endocrine disorders · 2023Pooled it
- The effect of allopurinol on cardiovascular outcomes in patients with type 2 diabetes: a systematic review.Hormones (Athens, Greece) · 2022Pooled it
- Effect of Empagliflozin on Serum Ferritin and Its Relationship With Inflammatory Markers in Prediabetic and Diabetic Patients.Journal of diabetes research · 2025Trial
- Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction - a post-hoc analysis of the EMMY trial.Cardiovascular diabetology · 2023 · on this mapTrial
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- Uncoupling Erythropoiesis from Cardiorenal Effects: SGLT2 Inhibition in Non-Diabetic Heart Failure.Medicina (Kaunas, Lithuania) · 2026Observational
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Comparison of renal outcomes between sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist in Japanese patients with type 2 diabetes and obesity.Clinical and experimental nephrology · 2026Article
- Interaction and Joint Effects of Inflammation and Triglyceride-Glucose (TyG) Index on Hyperuricemia Risk and the Mediating Role of TyG: A Cross-Sectional Study.Endocrinology, diabetes & metabolism · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Glucagon-Like Peptide-1 Receptor Agonists in Chronic Kidney Disease: Mechanisms and Clinical Perspectives.Kidney medicine · 2026Review
- Illuminating Glucose: How to Unveil Organ-Specific Insulin Resistance and Guide Metabolic Strategies in Diabetes.Diabetes/metabolism research and reviews · 2026Review
- Dapagliflozin attenuates diabetic renal fibrosis by inhibiting macrophage-myofibroblast transitionPeerJ · 2026Article
- Detection and Proinflammatory Effects of BTEX within the Human Atherosclerotic Plaque.Environmental science & technology · 2025Observational
- Dapagliflozin mitigates cognitive deficits in a rat model of chronic restrained stress by addressing insulin resistance and mitochondrial dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Sodium-glucose cotransporter-2 inhibitors and risk of autoimmune rheumatic diseases: population based cohort study.BMJ (Clinical research ed.) · 2025Article
- SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular-Kidney-Metabolic Syndrome.Biomedicines · 2025Review
19 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
13 authors at 3 institutions in 1 country.
Funding
Abstract
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (i) reduce cardiovascular and renal events in patients with and without type 2 diabetes (T2D). However, the underlying mechanisms are debated. Low-grade inflammation (LGI) is a key driver of vascular complications, suggested to be attenuated by SGLT-2i in animal models. Based on a specific working hypothesis, here we investigated the net effect of SGLT-2i on LGI in patients with T2D and the possible underlying mechanism. We enrolled patients with T2D treated either with a stable therapy with SGLT-2i or with other glucose-lowering drugs (GLD) (n = 43 per group after matching for a range of pro-inflammatory variables), and tested hs-CRP and interleukin (IL)-6 as primary variables of interest. Patients treated with SGLT-2i had lower circulating levels of IL-6, a prototypical marker of LGI, but also of uric acid and fasting insulin, compared with patients treated with other GLD. Then, to explore whether uric acid and insulin might mediate the effect of SGLT-2i on IL-6, we tested physiologically pertinent doses of these two molecules (i.e. 0.5 mM uric acid and 1 nM insulin) in two in vitro models of LGI, i.e. monocytes (THP-1) treated with LPS and endothelial cells (HUVEC) exposed to hyperglycaemia. Results from in vitro models supported a pro-inflammatory role for uric acid and its combination with insulin in monocytes and for uric acid alone in hyperglycaemia-stimulated endothelial cells. On the contrary, we observed no drug-intrinsic, anti-inflammatory effect for dapagliflozin, empagliflozin, and canagliflozin in the same models. Overall, these results suggest that SGLT-2i possess a tangible activity against LGI, an effect possibly mediated by their ability to lower uric acid and insulin concentrations and that juxtaposes other proposed mechanisms in explaining the observed benefit of this class on cardiovascular and renal endpoints.
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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 Socratic graph.