Trial reportDiabetologia2020
Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy.
Trial report in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03168295. Cited by 13 papers.
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SGLT2 INHIBITION AND STIMULATIION OF ENDOGENOUS GLUCOSE PRODUCTION Significance - PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria
Open the trial in the graphWho cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Effect of Dapagliflozin on Renal and Hepatic Glucose Kinetics in T2D and NGT Subjects.Diabetes · 2024Trial
- Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes.Diabetes care · 2024Trial
- Metabolic Reprogramming Coordinates Mannose and Glutamine Metabolism to Maintain Glucose Homeostasis During Glycosuria.bioRxiv : the preprint server for biology · 2026Article
- Inter-organ communication: pathways and targets to cardioprotection and neuro-protection. A report from the 12th Hatter Cardiovascular Institute workshop.Basic research in cardiology · 2025Article
- A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.eLife · 2024Article
- SGLT2 inhibitors: cardiorenal metabolic drugs for the ages.The Journal of clinical investigation · 2024Article
- Impact of dapagliflozin on metabolic phenotype, hormone levels, and fertility in female mice after prolonged high-fat diet.Frontiers in endocrinology · 2024Article
- Emergence of a New Glucoregulatory Mechanism for Glycemic Control With Dapagliflozin/Exenatide Therapy in Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2023Article
- New-Onset Diabetes Mellitus in Post-renal Transplant Patients on Tacrolimus and Mycophenolate: A Systematic Review.Cureus · 2022Review
- Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose.Diabetes care · 2022Article
- Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition.Current hypertension reports · 2022Review
- Type 2 diabetes subgroups and potential medication strategies in relation to effects on insulin resistance and beta-cell function: A step toward personalised diabetes treatment?Molecular metabolism · 2021Review
- Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis.Medical sciences (Basel, Switzerland) · 2020 · on this mapArticle
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe glucosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA
methodsThis was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30-65 years old, with a BMI of 25-35 kg/m
resultsTwenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 μmol min CONCLUSIONS/
interpretationIn nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal-hepatic axis).
trial registrationClinicalTrials.gov NCT03168295
fundingThis protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract.
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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.