ArticleDiabetes, obesity & metabolism2019
Sodium-glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter-organ crosstalk.
Article in Diabetes, obesity & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05975528 (Effect of Sodium-glucose Cotransporter-2 Inhibitor in Cellular Senescence in Patients With Cardiovascular Diseases or Advanced Type 2 Diabetes), which is not on this map. Cited by 37 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.
Effect of Sodium-glucose Cotransporter-2 Inhibitor in Cellular Senescence in Patients With Cardiovascular Diseases or Advanced Type 2 Diabetes
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.Journal of diabetes investigation · 2020Pooled it
- Basal insulin secretion capacity predicts the initial response and maximum levels of beta-hydroxybutyrate during therapy with the sodium-glucose co-transporter-2 inhibitor tofogliflozin, in relation to weight loss.Diabetes, obesity & metabolism · 2020Trial
- Urea cycle fumarate limits fibrosis post-myocardial infarction by reducing fibroblast mitochondrial adenosine triphosphate production.Cardiovascular research · 2026Article
- Prior SGLT2 Inhibitor and Metformin Use and Risk of Long COVID in Type 2 Diabetes: A Nationwide Population-Based Cohort Study.Infectious diseases and therapy · 2026Article
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Sodium-glucose cotransporter 2 inhibitors and the risk of kidney cancer among patients with type 2 diabetes: a population-based cohort study.BMC medicine · 2026Article
- The SGLT2 inhibitor checklist: a comprehensive review of perioperative and acute phase safety management.Frontiers in endocrinology · 2026Review
- Cardiometabolic and renal benefits of sodium-glucose cotransporter 2 inhibitors.Nature reviews. Endocrinology · 2025Review
- Ketone Body Induction: Insights into Metabolic Disease Management.Biomedicines · 2025Review
- Association between serum beta-hydroxybutyrate levels and risk of type 2 diabetes mellitus in patients with impaired fasting glucose.Nutrition & diabetes · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Impact of Dapagliflozin on Hepatic Lipid Metabolism and a Dynamic Model of Ketone Body Levels.The AAPS journal · 2025Article
- Emerging horizons: clinical applications and multifaceted benefits of SGLT-2 inhibitors beyond diabetes.Frontiers in cardiovascular medicine · 2025Review
- The Off-Target Cardioprotective Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors: An Overview.International journal of molecular sciences · 2024Review
- Sodium glucose cotransporter-2 inhibitors and heart disease: Current perspectives.World journal of cardiology · 2024Review
- SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.Cardiovascular research · 2024Review
- The SGLT2 inhibitor Empagliflozin promotes post-stroke functional recovery in diabetic mice.Cardiovascular diabetology · 2024Article
- Association between Impaired Ketogenesis and Metabolic-Associated Fatty Liver Disease.Biomolecules · 2023Review
- Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient.Heart failure reviews · 2023Review
- Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms.Cardiovascular diabetology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate sodium-glucose cotransporter 2 inhibitor (SGLT2i)-induced changes in ketogenic enzymes and transporters in normal and diabetic mice models. MATERIALS AND
methodsNormal mice were randomly assigned to receive either vehicle or SGLT2i (25 mg/kg/d by oral gavage) for 7 days. Diabetic mice were treated with vehicle, insulin (4.5 units/kg/d by subcutaneous injection) or SGLT2i (25 mg/kg/d by intra-peritoneal injection) for 5 weeks. Serum and tissues of ketogenic organs were analysed.
resultsIn both normal and diabetic mice, SGLT2i increased beta-hydroxybutyrate (BHB) content in liver, kidney and colon tissue, as well as in serum and urine. In these organs, SGLT2i upregulated mRNA expression of ketogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 and 3-hydroxy-3-methylglutaryl-coenzyme A lyase. Similar patterns were observed in the kidney, ileum and colon for mRNA and protein expression of sodium-dependent monocarboxylate transporters (SMCTs), which mediate the cellular uptake of BHB and butyrate, an important substrate for intestinal ketogenesis. In diabetic mice under euglycaemic conditions, SGLT2i increased major ketogenic enzymes and SMCTs, while insulin suppressed ketogenesis.
conclusionsSGLT2i increased systemic and tissue BHB levels by upregulating ketogenic enzymes and transporters in the liver, kidney and intestine, suggesting the integrated physiological consequences for ketone body metabolism of SGLT2i administration.
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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.