Trial reportDiabetes care2022
Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial.
Trial report in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 4 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 4 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- GLP1 receptor agonists and SGLT2 inhibitors for the prevention or delay of type 2 diabetes mellitus onset: a systematic review and meta-analysis.Frontiers in endocrinology · 2025Pooled it
- Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- A phase 2A/B randomized trial of metabolic modulators intranasal insulin and empagliflozin for MCI and early AD.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Effect of Empagliflozin on Serum Ferritin and Its Relationship With Inflammatory Markers in Prediabetic and Diabetic Patients.Journal of diabetes research · 2025Trial
- Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.Translational psychiatry · 2023Trial
- Impact of Fixed Combination of Metformin and Pioglitazone on Insulin Resistance of Patients with Type 2 Diabetes: Results of a Randomized Open-Label Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Trial
- Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese.JCI insight · 2022Trial
- Combination therapy with exenatide decreases the dapagliflozin-induced changes in brain responses to anticipation and consumption of palatable food in patients with type 2 diabetes: A randomized controlled trial.Diabetes, obesity & metabolism · 2022Trial
- Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2022Trial
- Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men.NeuroImage. Clinical · 2022Trial
- Hypothalamic insulin resistance in type 2 diabetes is localized to the posterior hypothalamus.JCI insight · 2026Article
- The role of metabolic disorders in major depressive disorder.Molecular biology reports · 2026Review
- Sodium-Glucose Cotransporter-2 Inhibitors in Mood Disorders: A Narrative Review of Mechanisms, Evidence, and Challenges.Neuropsychiatric disease and treatment · 2026Review
- Brain insulin resistance: a key pathological hub linking metabolic and neuropsychiatric comorbidities.Frontiers in aging neuroscience · 2026Review
- Targeting Neurodegeneration with SGLT2is: From Molecular Mechanisms to Clinical Implications.Molecular neurobiology · 2025Review
- Association between cerebral lesions and the severity of diabetic cardiovascular disease, retinopathy, and nephropathy-new lessons to learn from neuroimaging.Journal of endocrinological investigation · 2025Review
- Empagliflozin Protects Against Oxidative Stress in the Diabetic Brain by Inducing HPharmaceuticals (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInsulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance. RESEARCH DESIGN AND
methodsIn this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age 60 ± 9 years; BMI 31.5 ± 3.8 kg/m2) with prediabetes were randomized to receive 25 mg empagliflozin every day or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain.
resultsWe identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin-treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated the empagliflozin-induced decrease in fasting glucose and liver fat.
conclusionsOur results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.
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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.