Type 2 Diabetes MellitusLIGHT-MCINCT05313529
LIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes
A study testing Liraglutide, Empagliflozin and Linagliptin in people with Type 2 Diabetes Mellitus and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 5 sites in China.
Trial summary
This is an investigator-led prospective, randomized, open label, parallel study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the cognitive function in T2DM patients with mild cognitive impairment (MCI), consisting of a 48-week core study followed by a 28-week… Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Mild Cognitive Impairment
- What is being tested?
- Liraglutide, Empagliflozin and Linagliptin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 396 participants
- Where
- 5 sitesChina
- Study dates
- 8 Oct 2022to 1 Jul 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants aged ≥40 and ≤75 years, of any gender.
- Type 2 diabetes diagnosed according to the American Diabetes Association criteria
- Mild cognitive impairment diagnosed according to the established criteria
- Cognitive concern from the patient, or an informant or skilled clinicians
- Objective evidence of cognitive impairment: education-adjusted MoCA score ≤ 25 and ≥ 18; or ≥1.0 standard deviation below the mean of age- and education-specific groups on any cognitive subdomain
- Preservation of independence in daily living abilities: Barthel Index score ≥ 60
Show all 13Show fewer
- Absence of dementia
- Treatment with a stable glucose lowering regimen of metformin monotherapy (≥ 1,000 mg daily) or combination with sulfonylurea/glibenclamide/glycosidase inhibitor/basal insulin over the previous 3 months
- Glycosylated hemoglobin (HbA1c) during screening between ≥7.0% and ≤10.0%
- BMI of ≥ 19 kg/m2
- Education duration of ≥6 years
- Right-handed participants
- Understanding of the research procedures and methods, potential benefits and risks of the trial, and sign written informed consent
Who cannot join
- History of other dementia-related neurological diseases, depression within the past 2 years, developmental disorders, mania, depression, schizophrenia, etc.
- Significant nasal sinusitis, nasal cavity and sinus polyps, cranial or nasopharyngeal tumors and other space-occupying lesions, congenital diseases and trauma of the nose, maxillofacial area, and skull base that affect olfaction. Symptoms of upper respiratory tract infection on the day of MRI examination, including nasal congestion, rhinorrhea, fever, etc.
- Acute metabolic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemic coma within the previous 6 months
- Severe organ dysfunction of heart, liver, kidneys, and thyroid, including unstable angina, myocardial infarction, or grade II and above cardiac insufficiency within 3 months before screening; estimated glomerular filtration rate (eGFR) by CKD-EPI formula \<45 mL/min/1.73 m², alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater exceeding twice the upper limit of normal, hyperthyroidism or uncontrolled hypothyroidism
- History of medullary thyroid carcinoma, pancreatitis, multiple endocrine neoplasia syndrome type 2, recurrent urinary tract infections, severe gastrointestinal diseases or history of gastrointestinal surgery, history of malignant tumors
- With MRI contraindications, such as implanted metal prosthesis, claustrophobia, etc.
Show all 11Show fewer
- Females who are pregnant, lactating, breast feeding or of child bearing age without effective contraception
- Participated in other clinical trials within the previous 6 months
- Known or suspected allergy to the study drugs
- Received treatment with GLP-1RAs, dual GLP-1R/GCGR agonist, SGLT-2 inhibitors or DPP4 inhibitors in the past 3 months
- Known history of drug or alcohol abuse within the past 6 months
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Department of Endocrinology, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University
Changzhou, Jiangsu, 213000
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University
Nanjing, Jiangsu, 210000
Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
Department of Endocrinology, the Affiliated Jiangning Hospital of Nanjing Medical University
Nanjing, Jiangsu, 211100
Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University
Wuxi, Jiangsu, 214000
About this study
Official title: Effects of Liraglutide, Empagliflozin and Linagliptin on Mild Cognitive Impairment Remission in Type 2 Diabetes (LIGHT-MCI): A Multicentre, Randomised Controlled Trial With An Extension Phase
This is an investigator-led prospective, randomized, open label, parallel study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the cognitive function in T2DM patients with mild cognitive impairment (MCI), consisting of a 48-week core study followed by a 28-week extension phase.
Read the detailed description
The LIGHT-MCI trial is an investigator-led, prospective, randomized, open label, parallel, multi-center study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the MCI remission in T2DM patients with MCI inadequately controlled with metformin monotherapy. The trial consists of a 48-week core study followed by an extension phase through to 76 weeks and the investigators will screen in the outpatient and inpatient departments to enroll 396 patients (132 for each arm) totally with the inclusion and exclusion criteria. The patients will be randomized at a 1:1:1 ratio into Liraglutide, Empagliflozin and Linagliptin treatment group with a computer-generated random order. All patients will also continue on their existing dose and regimen of metformin throughout the study. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, body composition analysis, cognitive assessment, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all patients. During the treatment period, visits at 8-week intervals will be performed to evaluate the safety of drugs and adjust the dose of metformin if hypoglycaemia occurs; meanwhile, fasting and 2-hour postprandial plasma glucose assayed by fingerstick, physical examination, and olfactory test will be conducted. Participants who complete the 48-week core study will have the option to receive an additional 28 weeks of intervention after signing an extension consent form. At 48 and 76 weeks of treatment, all of the assessments will be performed again for all recruited subjects, including early withdrawal patients.
- Being tested
- Liraglutide, Empagliflozin, Linagliptin
- Keywords
- Functional MRI, cognition, Olfactory function, Liraglutide, Empagliflozin and Linagliptin
- Medical subject headings
- Diabetes Mellitus, Type 2, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called metformin
Liraglutide will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study
EmpagliflozinDrug
Also called metformin
Empagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.
LinagliptinDrug
Also called metformin
Iinagliptin will be initiated at 5mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Liraglutide will be titrated from 0.6mg/day to a final dose 1.8mg/day during the first 2 weeks, if well tolerated.
Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but liraglutide could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. Receives: Drug: Liraglutide |
| Empagliflozin | Experimental | Empagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study.
Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. Receives: Drug: Empagliflozin |
| linagliptin | Experimental | linagliptin will be initiated at 5mg/ day every morning. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but linagliptin could not be adjusted.
If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. Receives: Drug: Linagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mild cognitive impairment (MCI) remission rate
MCI mitigation is defined by three criteria: an education-adjusted score of the Montreal Cognitive Assessment (MoCA) ≥26, no cognitive deficits in any explored cognitive subdomain, including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory, evaluated by Trail-Making Test, Stroop Color-Word Test and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively, and preservation of ability to perform instrumental activity of daily living (IADL) with a Functional Activities Questionnaire (FAQ) score <5.
Measured: The core study spans from baseline to 48 weeks
Secondary outcomes (75)
Change in score of Mini-Mental State Examination (MMSE)
The MMSE contains a total of 30 items that assess orientation, registration, attention and calculation, recall, and language, with a score range from 0 to 30. Generally, a higher MMSE score reflects a better cognitive function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in score of MoCA
The MoCA (Chinese version) is a screening instrument for MCI comprised of 30 items to assess multiple cognitive domains (memory recall, visuospatial abilities, executive functions, attention, language, and orientation to time and place; scores range from 0 to 30, with higher scores indicating better cognitive function). Participants received one additional point if they had a MoCA score < 30 and 12 years or less of formal school education.
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in total score of RBANS
The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data, which consists of 12 task tests assessing 5 cognitive domains, namely immediate memory, visuospatial/ constructional, language, attention and delayed memory, with a score range from 40 to 160. A higher RBANS score reflects a better global cognitive function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of immediate memory
The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data. The RBANS includes 12 sub-tests that generate five age-adjusted index scores and a total score. The five indices include immediate memory (consisting of list learning and story memory tests), visuospatial/constructional domain (consisting of figure copying and line orientation tests), language (consisting of picture naming and semantic fluency tests), attention (consisting of digit span and coding tests) and delayed memory (consisting of list recall, story recall, figure recall and list recognition tests). Generally, a higher index score reflects a better cognitive subdomain function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of visuospatial/constructional
Measurements and instruments are the same as the RBANS index score of immediate memory.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of language
Measurements and instruments are the same as the RBANS index score of immediate memory.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of attention
Measurements and instruments are the same as the RBANS index score of immediate memory.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of delayed memory
Measurements and instruments are the same as the RBANS index score of immediate memory.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in aggregate time to test completion for Trail Making Test (TMT)
The TMT is a validated timed measure of processing speed, which consists of part A and part B (TMT-A and TMT-B). The time limits for performing the TMT-A and TMT-B are 180 and 300 seconds, respectively. Processing speed is estimated by the aggregate time in seconds to complete TMT-A and TMT-B such that less time indicate faster processing speed.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in aggregate time to test completion for Victoria Stroop Color-Word Test
The Victoria Stroop Color-Word Test is a well-known measure of executive function. There are three indices including Stroop-dot, Stroop-word and Stroop-color word in the test. The color task consists of colored dots; the word task comprises ordinary words that are unrelated to the meaning of color; the color-word task consists of words written in color that indicate the meaning of the color, but the color of these words differs from the meaning of the word itself. The participants were asked to quickly read the color of the dots or Chinese words on the cards. The sum of consuming time taken to read the three cards is used as an index of executive function performance. Less time indicates better executive function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total brain volume
Philips TX 3.0T superconducting clinical MRI will be used for magnetic resonance scanning (Philips Achieva 3T TX Medical Systems, Eindhoven, the Netherlands). T1 images were processed using Freesurfer software (version 8.1.0, https://surfer.nmr.mgh.harvard.edu) to calculate intracranial volume, total gray matter volume, total white matter volume, cerebrospinal fluid volume and volumes of 68 cortical and 14 subcortical regions based on the Desikan-Killiany atlas23. The total brain volume was calculated as the sum of the gray matter and white matter volumes.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total gray matter volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total white matter volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived cerebrospinal fluid volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived white matter hyperintensity volume (WMH)
Total white matter hyperintensity volume was measured from FLAIR images using the Lesion Segmentation Tool for Statistical Parametric Mapping (SPM) 12.0.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived frontal gray matter volume
Measurements and instruments are the same as total brain volume. Frontal gray matter volume was calculated as the sum of all frontal lobe regions parcellated by FreeSurfer (Desikan-Killiany atlas).
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived parietal gray matter volume
Measurements and instruments are the same as total brain volume. Parietal gray matter volume was calculated as the sum of all parietal lobe regions parcellated by FreeSurfer (Desikan-Killiany atlas).
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived temporal gray matter volume
Measurements and instruments are the same as total brain volume. Temporal gray matter volume was calculated as the sum of all temporal lobe regions parcellated by FreeSurfer (Desikan-Killiany atlas).
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived occipital gray matter volume
Measurements and instruments are the same as total brain volume. Occipital gray matter volume was calculated as the sum of all occipital lobe regions parcellated by FreeSurfer (Desikan-Killiany atlas).
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived insula gray matter volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived hippocampal volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived parahippocampal volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived entorhinal cortex volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived inferior parietal lobule volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived precuneus volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived cuneus volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived thalamus volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived caudate nucleus volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived putamen volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived pallidum volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived amygdala volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived accumbens volume
Measurements and instruments are the same as total brain volume.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in mean fractional anisotropy (FA) in white matter derived from diffusion tensor imaging (DTI)
Diffusion Toolbox in FMRIB Software Library (FSL, version 6.0.7, http://fsl.fmrib.ox.ac.uk/fsl/fslwiki) was used to process all DTI-scans, and generate FA maps. FA from DTI assessment is a global microstructural integrity measure, with higher value indicating better integrity.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in mean diffusivity (MD) in white matter derived from DTI
Measurement and instruments are the same as FA. MD describes the overall diffusion and motion of water molecules, with higher MD values reflect more water mobility.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in fractional volume of free water in white matter (FW-WM)
FW-WM maps were constructed from preprocessed diffusion-weighted images using a regularized bi-tensor model and the open-source software package Diffusion Imaging in Python (also known as Dipy) algorithm (https://dipy.org/). Elevated FW -WM suggests the stagnation of fluid drainage caused by glymphatic dysfunction.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in diffusion tensor image analysis along the perivascular space (DTI-ALPS) index
The ALPS index was analyzed on DTI images using a method developed and validated by Taoka et al. ALPS index = (mean (Dxxproj, Dxxassoc)) ∕ (mean (Dyyproj, Dzzassoc)). The ALPS indices in the bilateral hemispheres were calculated, respectively, and the mean was used in further analyses. The DTI-ALPS index is calculated from the diffusivity along the deep medullary vein at the level of the lateral ventricle body, as a measure of perivascular clearance activity in the human brain. It is validated as a non-invasive proxy for glymphatic functioning, with higher value indicating better function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in perivascular space volume fraction in white matter (PVSVF-WM)
PVSs were mapped from T2W images using an automated and highly reliable quantification method, following the pipeline of previous studies. The PVS volume fraction (PVSVF) = PVS volume/intracranial volume. The PVSVF-WM is a quantitative metric that reflects the distribution and dilatation of perivascular spaces within cerebral white matter. An elevated volume fraction may suggest impaired clearance function of brain interstitial fluid.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in functional MRI-derived odor-induced brain activation
Task-evoked activation was assessed using FSL FEAT (version 6.0.7), which use general linear modelling to estimate scent effects on brain activation. Bilateral parahippocampus, amygdala, piriform cortex, insula, orbitofrontal cortex, and hippocampus in Automated Anatomical Labeling templates and Brodmann areas 28 and 34 (entorhinal cortices) were extracted and merged as olfactory regions of interest (ROIs) (total cluster size 5,029 voxels) for further analyses.
Measured: from baseline to the 48 weeks of treatment.
Changes in plasma amyloid beta (Aβ)42/Aβ40 concentration
Plasma Aβ40 and Aβ42 concentration were measured using the Neurology 4-plex E assay kit from Quanterix.
Measured: from baseline to the 48 weeks of treatment.
Changes in plasma phosphorylated tau (p-tau)181 concentration
Plasma p-tau 181 concentration was measured using the p-Tau181 Advantage PLUS kit from Quanterix.
Measured: from baseline to the 48 weeks of treatment.
Changes in plasma p-tau 217 concentration
Plasma p-tau 217 concentration was measured using the ALZpath p-Tau217 Advantage PLUS kit from Quanterix.
Measured: from baseline to the 48 weeks of treatment.
Changes in plasma neurofilament light chain (NfL) concentration
Plasma NfL concentration was measured using the Neurology 4-plex E assay kit from Quanterix.
Measured: from baseline to the 48 weeks of treatment.
Changes in plasma glial fibrillary acidic protein (GFAP) concentration
Plasma GFAP concentration was measured using the Neurology 4-plex E assay kit from Quanterix.
Measured: from baseline to the 48 weeks of treatment.
Changes in resting-state functional MRI-derived brain network connectivity
The whole-brain network functional connectivity analysis was carried out using the CONN Toolbox (v.22.v2407). The Schaefer-Yeo 7-network functional atlas was used to parcellate the cortex into 400 volumetric functional parcels, and the Melbourne Subcortical Atlas was used to parcellate the subcortex into 54 functional nuclei, yielding a total of 454 regions. For each participant, the pre-processed resting-state fMRI time series was spatially averaged across all voxels composing each region, yielding an averaged time series for each region. The Pearson correlation coefficient was computed between all pairs of regions from the combined cortical and subcortical atlases to provide a measure of functional connectivity, yielding a 454*454 symmetric connectivity matrix for each individual.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in olfactory threshold scores
Olfactory Function Assessment by Computerized Testing (OLFACT®, Osmic Enterprises, Inc.) was administered to assess olfactory threshold, identification, and memory. The olfactory threshold test (score range, 1-14) was a forced-choice paradigm based on serial dilutions of N-butanol solutions. Higher scores indicate better olfactory function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in olfactory identification scores
Olfactory Function Assessment by Computerized Testing (OLFACT®, Osmic Enterprises, Inc.) was administered to assess olfactory threshold, identification, and memory. The olfactory identification (score 0-30) and memory (score 0-20) subtests consisted of two sequential phases separated by a 10-min interval. During task A, participants performed forced-choice identification of 10 distinct odors. In task B, they were presented with 20 odors (10 from task A and 10 novel distractors) and required to complete two tasks per odor: identify the odor, then classify it as 'old' or 'new' (relative to task A). Higher scores indicate better olfactory function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in olfactory memory scores
Olfactory Function Assessment by Computerized Testing (OLFACT®, Osmic Enterprises, Inc.) was administered to assess olfactory threshold, identification, and memory. The olfactory identification (score 0-30) and memory (score 0-20) subtests consisted of two sequential phases separated by a 10-min interval. During task A, participants performed forced-choice identification of 10 distinct odors. In task B, they were presented with 20 odors (10 from task A and 10 novel distractors) and required to complete two tasks per odor: identify the odor, then classify it as 'old' or 'new' (relative to task A). Higher scores indicate better olfactory function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in olfactory assessment total scores
The sum of the olfactory threshold, identification, and memory scores was referred to as the olfactory assessment total scores, which ranged from 0 to 64 points. Higher scores indicate better olfactory function.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in glycated haemoglobin (HbA1c) levels
Glycated haemoglobin A1c (HbA1c).
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting plasma glucose levels
Fasting plasma glucose.
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in 2-hour postprandial plasma glucose levels
2-hour postprandial plasma glucose.
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting insulin
Fasting insulin.
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting C-peptide levels
Fasting C-peptide levels.
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in 2-hour postprandial insulin
2-hour postprandial insulin.
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in 2-hour postprandial C-peptide levels
2-hour postprandial C-peptide levels.
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in pancreatic islet function (HOMA2-β)
Pancreatic islet function (HOMA2-β) was estimated from fasting C-peptide via HOMA2 Calculator (v2.2.3, http://www.dtu.ox.ac.uk/homacalculator/) .
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in insulin sensitivity (HOMA2-S)
Insulin sensitivity (HOMA2-S) was estimated from fasting C-peptide via HOMA2 Calculator (v2.2.3, http://www.dtu.ox.ac.uk/homacalculator/) .
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in insulin resistance indexes (HOMA2-IR)
Insulin resistance indexes (HOMA2-IR) was estimated from fasting C-peptide via HOMA2 Calculator (v2.2.3, http://www.dtu.ox.ac.uk/homacalculator/) .
Measured: from baseline to weeks 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting serum triglyceride levels
Fasting serum triglyceride levels
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting serum total cholesterol levels
Fasting serum total cholesterol levels
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting serum high-density lipoprotein-cholesterol levels
Fasting serum high-density lipoprotein-cholesterol levels
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in fasting serum low-density lipoprotein-cholesterol levels
Fasting serum low-density lipoprotein-cholesterol levels
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in visceral fat area
Visceral fat area was measured by Inbody 720 analyser.
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in percent body fat
Percent body fat was measured by Inbody 720 analyser.
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in liver stiffness
Liver stiffness measurement was quantified by FibroTouch® system
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in liver fat controlled attenuation parameter
Liver fat controlled attenuation parameter was quantified by FibroTouch® system
Measured: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in blood pressure
Systolic and diastolic blood pressure
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Change in body weight
Body weight
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Change in body mass index
Body mass index
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Change in waist circumference
Waist circumference
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Change in hip circumference
Hip circumference
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Change in waist to hip ratio
Waist circumference to hip circumference ratio
Measured: from baseline to week 48. (Measurements will be performed every 8 weeks until week 76, with data collected after week 48 will be analyzed and reported after the extension phase).
Changes in Barthel index
Basic activities of daily living (BADL) ability measured by the Barthel index. The Barthel Index (Chinese version) measures dependence in 10 basic personal activities of daily living such as showering, feeding, and walking. Ten items are rated, for a maximum score of 100 representing total independence. A "good" score is ≥ 60 points, which indicates that the patient is capable of basic self-care. Moderate dysfunction is defined as a score between 40 and 60, indicating that the patient needs help in daily life. Severe dysfunction is defined as a score between 20 and 40, indicating that the patient is significantly dependent on help in daily living. A score below 20 indicates a total disability in which the patient depends on help for all aspects of daily living. The measure is completed based on input from the direct care worker providing care to the participants on the day testing.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in FAQ score
Instrumental activities of daily living (IADL) ability measured by FAQ scores. The Functional Activities Questionnaire (FAQ, Chinese version) is a standardized assessment of instrumental activities of daily living such as preparing balanced meals and managing personal finances. Sum scores range from 0 to 30, with higher scores indicating worse function. Functional dependence is considered with scores ≥5 points.
Measured: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Mild cognitive impairment (MCI) remission rate at week76
MCI mitigation is defined by three criteria: an education-adjusted score of the Montreal Cognitive Assessment (MoCA) ≥26, no cognitive deficits in any explored cognitive subdomain, including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory, evaluated by Trail-Making Test, Stroop Color-Word Test and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively, and preservation of ability to perform instrumental activity of daily living (IADL) with a Functional Activities Questionnaire (FAQ) score <5.
Measured: from baseline to week 76 of treatment (the week 76 assessment will be analyzed and reported after the extension phase).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2022
- Study start8 Oct 2022
- Primary completion31 Dec 2025
- Study completion1 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 396 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Nanjing First Hospital, Nanjing Medical University, The Affiliated Jiangning Hospital of Nanjing Medical University, Wuxi People's Hospital, Changzhou No.2 People's Hospital
- Responsible party
- Principal investigator, Yan Bi, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Investigators
- Yan Bi, MD, PhD, Principal investigator, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05313529
- Sponsor's protocol ID
- 2022-LCYJ-ZD-03
- Acronym
- LIGHT-MCI
- Status last verified
- Aug 2026
- First submitted
- 19 Mar 2022
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data Availability: De-identified participant data may be shared with qualified researchers upon request, subject to review and approval. Access Conditions: Data requests require a valid research proposal and signed data use agreement. Approval is contingent on compliance with applicable laws and ethical guidelines. Timing: Data will become available after study completion and primary publication. Restrictions: Certain data types may be excluded due to privacy or regulatory requirements. Contact: Requests should be submitted to the study sponsor for consideration.
Publications
Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21.
PubMed 31221697Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2.
PubMed 29500313Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.
PubMed 35263425Yu C, Yang H, Zhang B, Chen S, Yang S, Li F, Zhu W, Zhai B, Wu T, Zhao S, Zhang W, Tong X, Duan Y, Zhang L, Chao Y, Wu J, Zhu X, Wang K, Ye X, Zhang X, Xu X, Cheng H, Liu J, Zhang J, Wang Y, Zhang Z, Yan W, Bi Y. Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase. BMJ Open. 2025 Aug 21;15(8):e095382. doi: 10.1136/bmjopen-2024-095382.
PubMed 40840993
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Liraglutide, Empagliflozin and Linagliptin on Mild Cognitive Impairment Remission in Type 2 Diabetes (LIGHT-MCI): A Multicentre, Randomised Controlled Trial With An Extension Phase
- ClinicalTrials.gov ID
- NCT05313529
- Acronym / sponsor ID
- LIGHT-MCI / 2022-LCYJ-ZD-03
- Keywords
- Functional MRI, cognition, Olfactory function, Liraglutide, Empagliflozin and Linagliptin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 396 participants (actual)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Collaborators
- Nanjing First Hospital, Nanjing Medical University, The Affiliated Jiangning Hospital of Nanjing Medical University, Wuxi People's Hospital, Changzhou No.2 People's Hospital
- Study start
- 8 Oct 2022 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 1 Jul 2026 (actual)
- First posted
- 6 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an investigator-led prospective, randomized, open label, parallel study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the cognitive function in T2DM patients with mild cognitive impairment (MCI), consisting of a 48-week core study followed by a 28-week extension phase.
Detailed description
The LIGHT-MCI trial is an investigator-led, prospective, randomized, open label, parallel, multi-center study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the MCI remission in T2DM patients with MCI inadequately controlled with metformin monotherapy. The trial consists of a 48-week core study followed by an extension phase through to 76 weeks and the investigators will screen in the outpatient and inpatient departments to enroll 396 patients (132 for each arm) totally with the inclusion and exclusion criteria. The patients will be randomized at a 1:1:1 ratio into Liraglutide, Empagliflozin and Linagliptin treatment group with a computer-generated random order. All patients will also continue on their existing dose and regimen of metformin throughout the study. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, body composition analysis, cognitive assessment, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all patients. During the treatment period, visits at 8-week intervals will be performed to evaluate the safety of drugs and adjust the dose of metformin if hypoglycaemia occurs; meanwhile, fasting and 2-hour postprandial plasma glucose assayed by fingerstick, physical examination, and olfactory test will be conducted. Participants who complete the 48-week core study will have the option to receive an additional 28 weeks of intervention after signing an extension consent form. At 48 and 76 weeks of treatment, all of the assessments will be performed again for all recruited subjects, including early withdrawal patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: LiraglutideLiraglutide will be titrated from 0.6mg/day to a final dose 1.8mg/day during the first 2 weeks, if well tolerated. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but liraglutide could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. |
| Empagliflozin | Experimental | Drug: EmpagliflozinEmpagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. |
| linagliptin | Experimental | Drug: Linagliptinlinagliptin will be initiated at 5mg/ day every morning. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but linagliptin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants aged ≥40 and ≤75 years, of any gender.
- Type 2 diabetes diagnosed according to the American Diabetes Association criteria
- Mild cognitive impairment diagnosed according to the established criteria
- Treatment with a stable glucose lowering regimen of metformin monotherapy (≥ 1,000 mg daily) or combination with sulfonylurea/glibenclamide/glycosidase inhibitor/basal insulin over the previous 3 months
- Glycosylated hemoglobin (HbA1c) during screening between ≥7.0% and ≤10.0%
Key exclusion criteria (11 listed)
- History of other dementia-related neurological diseases, depression within the past 2 years, developmental disorders, mania, depression, schizophrenia, etc.
- Significant nasal sinusitis, nasal cavity and sinus polyps, cranial or nasopharyngeal tumors and other space-occupying lesions, congenital diseases and trauma of the nose, maxillofacial area, and skull base that affect olfaction. Symptoms of upper respiratory tract infection on the day of MRI examination, including nasal congestion, rhinorrhea, fever, etc.
- Acute metabolic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemic coma within the previous 6 months
- Severe organ dysfunction of heart, liver, kidneys, and thyroid, including unstable angina, myocardial infarction, or grade II and above cardiac insufficiency within 3 months before screening; estimated glomerular filtration rate (eGFR) by CKD-EPI formula \<45 mL/min/1.73 m², alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater exceeding twice the upper limit of normal, hyperthyroidism or uncontrolled hypothyroidism
- History of medullary thyroid carcinoma, pancreatitis, multiple endocrine neoplasia syndrome type 2, recurrent urinary tract infections, severe gastrointestinal diseases or history of gastrointestinal surgery, history of malignant tumors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideAlso: metforminLiraglutide will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study | Drug | Liraglutide |
| EmpagliflozinAlso: metforminEmpagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study. | Drug | Empagliflozin |
| LinagliptinAlso: metforminIinagliptin will be initiated at 5mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study. | Drug | linagliptin |
Primary outcome
Mild cognitive impairment (MCI) remission rate
Time frame: The core study spans from baseline to 48 weeks
MCI mitigation is defined by three criteria: an education-adjusted score of the Montreal Cognitive Assessment (MoCA) ≥26, no cognitive deficits in any explored cognitive subdomain, including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory, evaluated by Trail-Making Test, Stroop Color-Word Test and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively, and preservation of ability to perform instrumental activity of daily living (IADL) with a Functional Activities Questionnaire (FAQ) score <5.
75 secondary outcomes
Change in score of Mini-Mental State Examination (MMSE)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in score of MoCA
Time frame: from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in total score of RBANS
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of immediate memory
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of visuospatial/constructional
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of language
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of attention
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in the RBANS index score of delayed memory
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in aggregate time to test completion for Trail Making Test (TMT)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Change in aggregate time to test completion for Victoria Stroop Color-Word Test
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total brain volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived total white matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived cerebrospinal fluid volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived white matter hyperintensity volume (WMH)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived frontal gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived parietal gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived temporal gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived occipital gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived insula gray matter volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived hippocampal volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived parahippocampal volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived entorhinal cortex volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived inferior parietal lobule volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived precuneus volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived cuneus volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived thalamus volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived caudate nucleus volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived putamen volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived pallidum volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived amygdala volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in MRI-derived accumbens volume
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in mean fractional anisotropy (FA) in white matter derived from diffusion tensor imaging (DTI)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in mean diffusivity (MD) in white matter derived from DTI
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in fractional volume of free water in white matter (FW-WM)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in diffusion tensor image analysis along the perivascular space (DTI-ALPS) index
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in perivascular space volume fraction in white matter (PVSVF-WM)
Time frame: from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).
Changes in functional MRI-derived odor-induced brain activation
Time frame: from baseline to the 48 weeks of treatment.
Changes in plasma amyloid beta (Aβ)42/Aβ40 concentration
Time frame: from baseline to the 48 weeks of treatment.
Changes in plasma phosphorylated tau (p-tau)181 concentration
Time frame: from baseline to the 48 weeks of treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Results publication: PubMed 31221697Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21.
- Results publication: PubMed 29500313Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2.
- Results publication: PubMed 35263425Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.
- Derived from this study: PubMed 40840993Yu C, Yang H, Zhang B, Chen S, Yang S, Li F, Zhu W, Zhai B, Wu T, Zhao S, Zhang W, Tong X, Duan Y, Zhang L, Chao Y, Wu J, Zhu X, Wang K, Ye X, Zhang X, Xu X, Cheng H, Liu J, Zhang J, Wang Y, Zhang Z, Yan W, Bi Y. Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase. BMJ Open. 2025 Aug 21;15(8):e095382. doi: 10.1136/bmjopen-2024-095382.
- Individual participant dataSharing planned: Yes. Data Availability: De-identified participant data may be shared with qualified researchers upon request, subject to review and approval. Access Conditions: Data requests require a valid research proposal and signed data use agreement. Approval is contingent on compliance with applicable laws and ethical guidelines. Timing: Data will become available after study completion and primary publication. Restrictions: Certain data types may be excluded due to privacy or regulatory requirements. Contact: Requests should be submitted to the study sponsor for consideration.
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yan Bi, MD, PhD principal investigator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liraglutide, Empagliflozin and Linagliptin in people with Type 2 Diabetes Mellitus and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mild cognitive impairment (MCI) remission rate (time frame: The core study spans from baseline to 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05313529, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.