Trial reportBritish journal of clinical pharmacology2013
The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus.
Trial report in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00554450. Cited by 46 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.
The Pharmacodynamics, Pharmacokinetics, and Safety of Dapagliflozin in Type 2 Diabetic Subjects With Mild, Moderate, and Severe Renal Impairment
Open the trial in the graphEffect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- The Urinary Glucose Excretion by Sodium-Glucose Cotransporter 2 Inhibitor in Patients With Different Levels of Renal Function: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2021Pooled it
- Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial.European heart journal · 2022Trial
- Evaluation of the Pharmacokinetics and Exposure-Response Relationship of Dapagliflozin in Patients without Diabetes and with Chronic Kidney Disease.Clinical pharmacokinetics · 2021Trial
- Physiologically-Based Pharmacokinetic Modeling of the Drug-Drug Interaction of the UGT Substrate Ertugliflozin Following Co-Administration with the UGT Inhibitor Mefenamic Acid.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Trial
- Pharmacokinetics and Pharmacodynamics of Luseogliflozin, a Selective SGLT2 Inhibitor, in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment.Clinical pharmacology in drug development · 2018Trial
- Impact of Reduced Renal Function on the Glucose-Lowering Effects of Luseogliflozin, a Selective SGLT2 Inhibitor, Assessed by Continuous Glucose Monitoring in Japanese Patients with Type 2 Diabetes Mellitus.Advances in therapy · 2016Trial
- Trial
- Pharmacokinetic and pharmacodynamic profiles of canagliflozin in Japanese patients with type 2 diabetes mellitus and moderate renal impairment.Clinical drug investigation · 2014Trial
- Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control.Kidney international · 2014Trial
- Sex Differences in Antiarrhythmic Effects of Empagliflozin: The EMPA-ICD Trial Subanalysis.JACC. Asia · 2026Article
- A Physiologically Based Pharmacokinetic and Pharmacodynamic (PBPK/PD) Model of Dapagliflozin in Type 2 Diabetes Mellitus: The Effect of Dosing, Hepatorenal Impairment, and Food.Pharmaceutics · 2026Article
- Multi-dimensional roles of sodium-glucose cotransporter 2 inhibitors: beyond hypoglycemic and cardiorenal protection.Frontiers in endocrinology · 2025Review
- Physiologically based pharmacokinetic model of sodium-glucose cotransporter 2 inhibitors predicted pharmacokinetics and pharmacodynamics to explore dosage regimen for patients with type 2 diabetes mellitus and renal insufficiency.Frontiers in pharmacology · 2025Article
- Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease.The AAPS journal · 2024Article
- Exposure-Response Analysis of the Sodium-Glucose Cotransporter-2 Inhibitors Dapagliflozin and Empagliflozin on Kidney Hemodynamics in Patients with Type 2 Diabetes.Journal of personalized medicine · 2023Article
- Pharmacokinetics under the COVID-19 storm.British journal of clinical pharmacology · 2023Article
- Effect ofFrontiers in pharmacology · 2023Article
- Dapagliflozin Prevents High-Glucose-Induced Cellular Senescence in Renal Tubular Epithelial Cells.International journal of molecular sciences · 2022Article
- Potential Safety Issues with Use of Sodium-Glucose Cotransporter 2 Inhibitors, Particularly in People with Type 2 Diabetes and Chronic Kidney Disease.Drug safety · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AIM(S): This study assessed the effect of differences in renal function on the pharmacokinetics and pharmacodynamics of dapagliflozin, a renal sodium glucose co-transporter-2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus (T2DM).
methodsA single 50 mg dose of dapagliflozin was used to assess pharmacokinetics and pharmacodynamics in five groups: healthy non-diabetic subjects; patients with T2DM and normal kidney function and patients with T2DM and mild, moderate or severe renal impairment based on estimated creatinine clearance. Subsequently, 20 mg once daily multiple doses of dapagliflozin were evaluated in the patients with T2DM. Formation rates of dapagliflozin 3-O-glucuronide (D3OG), an inactive metabolite, were evaluated using human isolated kidney and liver microsomes.
resultsPlasma concentrations of dapagliflozin and D3OG were incrementally increased with declining kidney function. Steady-state Cmax for dapagliflozin were 4%, 6% and 9% higher and for D3OG were 20%, 37% and 52% higher in patients with mild, moderate and severe renal impairment, respectively, compared with normal function. AUC(0,τ) was likewise higher. D3OG formation in kidney microsomes was three-fold higher than in liver microsomes and 109-fold higher than in intestine microsomes. Compared with patients with normal renal function, pharmacodynamic effects were attenuated with renal impairment. Steady-state renal glucose clearance was reduced by 42%, 83% and 84% in patients with mild, moderate or severe renal impairment, respectively.
conclusionsThese results indicate that both kidney and liver significantly contribute to dapagliflozin metabolism, resulting in higher systemic exposure with declining kidney function. Dapagliflozin pharmacodynamics in diabetic subjects with moderate to severe renal impairment are consistent with the observation of reduced efficacy in this patient population.
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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 OpenQuestion graph.