Evidence map›Paper›PMID 41619161›Full record

Trial reportJournal of endocrinological investigation2026

Henagliflozin enhances frontal neural activation and cognitive function versus gliclazide in type 2 diabetes patients with mild cognitive impairment: A 16-week randomized controlled trial.

Yining Chao, Jingyi Jiao, Bing Zhang, Jing Sun, Xuewei Tong, Huijie Yang, Tianyu Wu, Zhou Zhang, Yan Bi

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of endocrinological investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06085703 (A Prospective, Randomized, Open Label, Parallel, 6-month Study to Explore and Evaluate the Therapeutic Effects of Henagliflozin on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in T2DM Patients With Mild Cognitive Impairment.), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT06085703 nacompletednot on this map

A Prospective, Randomized, Open Label, Parallel, 6-month Study to Explore and Evaluate the Therapeutic Effects of Henagliflozin on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in T2DM Patients With Mild Cognitive Impairment.

TypeinterventionalSponsorThe Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolRan2024 to 2025Enrolled24ConditionsType 2 Diabetes Mellitus, Mild Cognitive ImpairmentArmsHenagliflozin, Gliclazide
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yining Chao *Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Jingyi Jiao *Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Bing Zhang *Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Jing Sun *Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Xuewei TongDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Huijie YangDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Tianyu WuDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Zhou ZhangDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. zhangzhou@smail.nju.edu.cn.ORCID http://orcid.org/0000-0003-2386-6141
Yan BiDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. biyan@nju.edu.cn.ORCID http://orcid.org/0000-0003-3914-7854

Funding

Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0523200the Jiangsu Provincial Medical Key Discipline Cultivation Unit JSDW202201the Nanjing Health Science and Technology Development Project ZKX24023the National Chinese-Western Medicine Clinical Collaboration Project for Major Difficult Diseases 2024-92the National Natural Science Foundation of China Grant Awards 82030026the National Natural Science Foundation of China Grant Awards 82270883the National Natural Science Foundation of China Grant Awards 82450002the National Natural Science Foundation of China Grant Awards 82470866the Natural Science Foundation of Jiangsu Province of China BK20241721YLHR Diabetes Metabolism Research Fund Project of China International Medical Foundation Z-2017-26-2202-4
6 · The paper itself

Abstract

aimsHead-to-head comparisons of neuroprotective efficacy of glucose-lowering agents remain lacking in type 2 diabetes (T2D) patients with mild cognitive impairment (MCI). Here, we investigated the effects of henagliflozin or gliclazide on brain functional alterations and cognitive changes in these patients. MATERIALS AND

methodsTwenty-four T2D patients with MCI were randomized (1:1) to receive henagliflozin or gliclazide treatment for 16 weeks. We assessed anthropometric and metabolic profiling, global and domain-specific cognitive testing, olfactory performance, and structural and functional magnetic resonance imaging (fMRI) at baseline and follow-up. The primary outcome was the between-group difference in odor-task fMRI activation at week 16.

resultsTreatment with henagliflozin for 16 weeks significantly increased odor-task fMRI activation in the left frontal white matter (Gaussian random field corrected) compared to gliclazide. Subsequent seed-based analysis revealed reduced functional connectivity to the left middle frontal gyrus, suggesting altered frontal network integration. These functional brain alterations were accompanied by significant improvements in global cognition (Montreal Cognitive Assessment [MoCA]: Δ + 2.1 vs. Δ − 0.2, P = 0.002) and delayed memory (Δ + 5.7 vs. Δ − 2.7, P = 0.012) in henagliflozin compared to gliclazide. Exploratory analyses suggested potential associations between concomitant metabolic improvements and cognitive/neuroimaging alterations, which merit further investigation.

conclusionsOur study showed that henagliflozin enhanced frontal brain activity and improved cognition (global and domain-specific: delayed memory) in T2D patients with MCI over 16 weeks, whereas gliclazide did not. These findings highlight the potential of henagliflozin for cognitive protection in this high-risk population. REGISTRATION: ClinicalTrials.gov (NCT06085703).

Indexed as

CognitionCognitive DysfunctionDiabetes Mellitus, Type 2Frontal LobeGliclazideAgedCognitive EnhancementFemaleFollow-Up StudiesHumansHypoglycemic AgentsMagnetic Resonance ImagingMaleMiddle AgedPrognosisGliclazideHypoglycemic AgentsCognitive functionFunctional magnetic resonance imagingMild cognitive impairmentRandomized controlled trialSGLT2 inhibitorType 2 diabetes

Identifiers

PMID41619161

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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.