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LIGHT-MCI
Active not recruitingPhase NALIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes
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
Asset
Liraglutide
Subcutaneous · GLP-1 agonist
Listed sites
5
Recruiting sites
—
Enrollment
396
estimated
Study population
Alzheimer's / cognition, Type 2 diabetes
Key I/E criteria
•BMI ≥19•HbA1c 7-10%
Primary endpoint
•Mild cognitive impairment (MCI) remission rate
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Participants aged ≥40 and ≤75 years, of any gender.
2. Type 2 diabetes diagnosed according to the American Diabetes Association criteria
3. Mild cognitive impairment diagnosed according to the established criteria
1. Cognitive concern from the patient, or an informant or skilled clinicians
2. 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
3. Preservation of independence in daily living abilities: Barthel Index score ≥ 60
4. Absence of dementia
4. 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
5. Glycosylated hemoglobin (HbA1c) during screening between ≥7.0% and ≤10.0%
6. BMI of ≥ 19 kg/m2
7. Education duration of ≥6 years
8. Right-handed participants
9. Understanding of the research procedures and methods, potential benefits and risks of the trial, and sign written informed consent
Exclusion criteria
1. History of other dementia-related neurological diseases, depression within the past 2 years, developmental disorders, mania, depression, schizophrenia, etc.
2. 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.
3. Acute metabolic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemic coma within the previous 6 months
4. 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
5. 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
6. With MRI contraindications, such as implanted metal prosthesis, claustrophobia, etc.
7. Females who are pregnant, lactating, breast feeding or of child bearing age without effective contraception
8. Participated in other clinical trials within the previous 6 months
9. Known or suspected allergy to the study drugs
10. Received treatment with GLP-1RAs, dual GLP-1R/GCGR agonist, SGLT-2 inhibitors or DPP4 inhibitors in the past 3 months
11. Known history of drug or alcohol abuse within the past 6 months
Endpoints (76)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Weight & body composition
7 endpointsChange in visceral fat area
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).
Visceral fat, change
change from baseline, improvement
Change in percent body fat
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).
Total fat mass
change from baseline, improvement
Change in body weight
Time frame: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).
Body weight, absolute change (kg)
change from baseline, improvement
Change in body mass index
Time frame: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).
BMI, change
change from baseline, improvement
Change in waist circumference
Time frame: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).
Waist circumference, change
change from baseline, improvement
Change in hip circumference
Time frame: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 from baseline, improvement
Change in waist to hip ratio
Time frame: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 from baseline, improvement
Glycemic / diabetes
10 endpointsChange in glycated haemoglobin (HbA1c) levels
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).
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Change in fasting plasma glucose levels
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).
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Change in 2-hour postprandial plasma glucose levels
Time frame: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).
Postprandial glucose
change from baseline, improvement
Change in fasting insulin
Time frame: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 from baseline, improvement
Change in fasting C-peptide levels
Time frame: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 from baseline, improvement
Change in 2-hour postprandial insulin
Time frame: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 from baseline, improvement
Change in 2-hour postprandial C-peptide levels
Time frame: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).
C-peptide AUC
change from baseline, improvement
Change in pancreatic islet function (HOMA2-β)
Time frame: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 from baseline, improvement
Change in insulin sensitivity (HOMA2-S)
Time frame: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).
HOMA-IR (insulin sensitivity)
change from baseline, improvement
Change in insulin resistance indexes (HOMA2-IR)
Time frame: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).
HOMA-IR (insulin sensitivity)
change from baseline, improvement
MASH / liver
2 endpointsChange in liver stiffness
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).
Liver stiffness (VCTE), change
change from baseline, improvement
Change in liver fat controlled attenuation parameter
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).
change from baseline, improvement
Cardiometabolic biomarkers
5 endpointsChange in fasting serum triglyceride levels
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).
Triglycerides, change
change from baseline, improvement
LOINC 2571-8
Change in fasting serum total cholesterol levels
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).
Total cholesterol, change
change from baseline, improvement
LOINC 2093-3
Change in fasting serum high-density lipoprotein-cholesterol levels
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).
HDL-C, change
change from baseline, improvement
LOINC 2085-9
Change in fasting serum low-density lipoprotein-cholesterol levels
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).
LDL-C, change
change from baseline, improvement
LOINC 13457-7
Change in blood pressure
Time frame: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 from baseline, improvement
Patient-reported / QoL
1 endpointChanges in Barthel 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).
change from baseline, improvement
Other clinical outcomes
44 endpointsMild cognitive impairment (MCI) remission rate
Time frame:The core study spans from baseline to 48 weeks
categorical status, improvement
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).
change from baseline, improvement
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).
change from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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 from baseline, improvement
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).
change from baseline, improvement
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, improvement
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, descriptive
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).
change from baseline, improvement
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).
change from baseline, improvement
Changes in functional MRI-derived odor-induced brain activation
Time frame:from baseline to the 48 weeks of treatment.
change from baseline, descriptive
Changes in plasma amyloid beta (Aβ)42/Aβ40 concentration
Time frame:from baseline to the 48 weeks of treatment.
change from baseline, descriptive
Changes in resting-state functional MRI-derived brain network connectivity
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 from baseline, descriptive
Changes in olfactory threshold scores
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 from baseline, improvement
Changes in olfactory identification scores
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 from baseline, improvement
Changes in olfactory memory scores
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 from baseline, improvement
Changes in olfactory assessment total scores
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 from baseline, improvement
Changes in FAQ score
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 from baseline, improvement
Mild cognitive impairment (MCI) remission rate at week76
Time frame:from baseline to week 76 of treatment (the week 76 assessment will be analyzed and reported after the extension phase).
categorical status, improvement
Other (unclassified)
7 endpointsChanges 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).
change from baseline, descriptive
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).
change from baseline, improvement
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).
change from baseline, improvement
Changes in plasma phosphorylated tau (p-tau)181 concentration
Time frame:from baseline to the 48 weeks of treatment.
concentration, descriptive
Changes in plasma p-tau 217 concentration
Time frame:from baseline to the 48 weeks of treatment.
concentration, descriptive
Changes in plasma neurofilament light chain (NfL) concentration
Time frame:from baseline to the 48 weeks of treatment.
concentration, descriptive
Changes in plasma glial fibrillary acidic protein (GFAP) concentration
Time frame:from baseline to the 48 weeks of treatment.
concentration, descriptive
Publications (4)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- BMJ open2025 Aug 21PMID40840993doi:10.1136/bmjopen-2024-095382via clinicaltrials gov reference derived + pubmed nct search
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.