Trial reportThe Journal of clinical investigation2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It reports registered trial NCT02113241. Cited by 387 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.
Effect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy
SGLT-2 Inhibitor Empagliflozin Effects on Appetite and Weight Regulation: A Randomised Double-blind Placebo-controlled Trial (The SEESAW Study)
Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects With Type 2 Diabetes Mellitus on Previous Metformin Treatment
Who cites it
387 citing papers in PubMed, 3 syntheses or guidelines pooled it, 771 citations in OpenAlex.
- Meta-analysis of the effect of sodium-dependent glucose transporter 2 inhibitors on C-reactive protein in type 2 diabetes.Medicine · 2022Pooled it
- GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- The efficacy of dapagliflozin for type 1 diabetes: a meta-analysis of randomized controlled studies.African health sciences · 2021Pooled it
- Trial
- Efficacy and safety of pioglitazone versus dapagliflozin as an add-on to metformin and alogliptin combination therapy: the EPIDOTE study.Scientific reports · 2025Trial
- Efficacy and Safety of Triple Fixed Dose Combination of Dapagliflozin + Sitagliptin + Metformin IR in Indian Patients with Type 2 Diabetes Mellitus: A Randomized, Phase 3 Study in Comparison with Dual FDC Sitagliptin + Metformin IR.Advances in therapy · 2025Trial
- Effects of SGLT2 inhibition on insulin use in CKD and type 2 diabetes: insights from the CREDENCE trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025 · on this mapTrial
- Effect of dapagliflozin on blood and breath ketones during supervised insulin withdrawal in adults with type 1 diabetes: A randomized crossover trial.Diabetes, obesity & metabolism · 2025Trial
- Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Effects of Ipragliflozin on Skeletal Muscle Adiposity in Patients with Diabetes and Metabolic Dysfunction-associated Steatotic Liver Disease.Internal medicine (Tokyo, Japan) · 2025Trial
- Combination SGLT2 Inhibitor and Glucagon Receptor Antagonist Therapy in Type 1 Diabetes: A Randomized Clinical Trial.Diabetes care · 2025Trial
- Trial
- 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
- The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator.Cardiovascular diabetology · 2024Trial
- Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial.Diabetes & metabolism journal · 2023Trial
- Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension.Diabetes & metabolism journal · 2023Trial
- Changes in glycemic control and skeletal muscle mass indices after dapagliflozin treatment in individuals with type 1 diabetes mellitus.Journal of diabetes investigation · 2023Trial
- Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open-label, crossover, active-comparator FIORE trial.Diabetes, obesity & metabolism · 2022Trial
- Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report.Cardiovascular diabetology · 2022Trial
327 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.
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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.