ArticleCardiovascular drugs and therapy2017
SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor.
Article in Cardiovascular drugs and therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05618223 (Dapagliflozin Effect on Rheumatic Mitral Stenosis), which is not on this map. Cited by 220 papers, 3 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.
Dapagliflozin Effect on Rheumatic Mitral Stenosis
Open the trial in the graphWho cites it
220 citing papers in PubMed, 3 syntheses or guidelines pooled it, 361 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
- Genomic insights about the effect of sodium-glucose cotransporter 2 inhibitors: a systematic review.Frontiers in genetics · 2025Pooled it
- Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review.Cardiovascular ultrasound · 2019Pooled it
- Review
- Additive Effects of Quercetin-RichPharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting Inflammation in Obesity and the Cardiovascular-Kidney-Metabolic Syndrome Spectrum: A Narrative Review.Obesity facts · 2026Review
- Oxidative Stress in Diabetic Cardiomyopathy: Molecular Mechanisms, Current Treatment and Therapeutic Potential of Plant Antioxidants.Antioxidants (Basel, Switzerland) · 2026Review
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- Inflammatory signalling in diabetic cardiomyopathy: molecular mechanisms and potential therapeutic strategies.Nature reviews. Cardiology · 2026Review
- Comorbidity-Driven Inflammation in HFpEF: Immune Profiling and Therapeutic Targets.Current heart failure reports · 2026Review
- Empagliflozin Attenuates Cardiac Fibrosis by Suppressing Fibroblast-Mediated C-C Motif Chemokine Ligand 2 Expression.Journal of the American Heart Association · 2026Article
- [Immunometabolic disorders in type 2 diabetes mellitus mediated by NLRP3 inflammasome activation and methods of pharmacological correction thereof].Problemy endokrinologii · 2026Review
- Article
- Expanding the scope of SGLT inhibitors in underrepresented cardiac populations: from pathophysiology to clinical evidence.Frontiers in cardiovascular medicine · 2026Review
- Potential Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors in Regulating Cardiac and Renal Fibrosis.Cardiorenal medicine · 2026Review
- Diabetic cardiomyopathy: Mechanistic insights on molecular pathways and emerging therapeutic approaches.Heart failure reviews · 2025Review
- Novel Insights into the Causal Relationship between Antidiabetic Drugs and Adverse Perinatal Outcomes: A Mendelian Randomization Study.Diabetes & metabolism journal · 2025Article
- Comparison of the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiac Fibroblast Properties.International journal of molecular sciences · 2025Article
- Sodium-glucose cotransporter-2 inhibitors and risk of autoimmune rheumatic diseases: population based cohort study.BMJ (Clinical research ed.) · 2025Article
- Guidelines for diet-induced models of cardiometabolic syndrome.American journal of physiology. Heart and circulatory physiology · 2025Review
160 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
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor) attenuates the deterioration of heart function Nlrp3 and inflammasome activation in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on cardiofibroblasts in vitro.
methodsType 2 diabetic (BTBR ob/ob) and wild-type (WT) mice received vehicle, Dapa, or Dapa+Saxa for 8 weeks. Glucose tolerance test and echocardiogram were performed. Cardiofibroblasts from WT and BTBR hearts were incubated with Dapa and exposed to LPS.
resultsLeft ventricular ejection fraction (LVEF) was 81 ± 1% in the WT and 53 ± 1% in the T2D-cont mice. Dapa and Dapa+Saxa improved LVEF to 68 ± 1 and 74.6 ± 1% in the BTBR mice (p < 0.001). The mRNA levels of NALP3, ASC, IL-1β, IL-6, caspase-1, and TNFα were significantly higher in the BTBR compared to the WT hearts; and Dapa and Dapa+Saxa significantly attenuated these levels. Likewise, protein levels of NLRP3, TNFα, and caspase-1 were higher in the BTBR compared to the WT hearts and Dapa, and to a greater extent Dapa+Saxa, attenuated the increase in the BTBR mice. Collagen-1 and collagen-3 mRNA levels significantly increased in the BTBR mice and these increases were attenuated by Dapa and Dapa+Saxa. P-AMPK/total-AMPK ratio was significantly lower in the BTBR mice than in the WT mice. Dapa and Dapa+Saxa equally increased the ratio in the BTBR mice. This in vitro study showed that NALP3, ASC, IL-1β, and caspase-1 mRNA levels were higher in the BTBR cardiofibroblasts and attenuated with Dapa. The effect was AMPK-dependent and SGLT1-independent.
conclusionsDapa attenuated the activation of the inflammasome, fibrosis, and deterioration of LVEF in BTBR mice. The anti-inflammatory, anti-fibrotic effects are likely SGLT2- and glucose-lowering-independent, as they were replicated in the in vitro model. The effects on remodeling were augmented when Saxa was added to Dapa. Yet, adding Saxa to Dapa did not result in a greater effect on myocardial fibrosis and collagen levels.
Indexed as
Identifiers
What Socratic 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 Socratic graph.