← Trials/Trial dossier/NCT07083154
GLP-1/GCG Dual Agonist in Type 2 Diabetes With Early Dementia (LIGHT-COG Study)
Efficacy, Safety, and Tolerability of a GLP-1/GCG Dual Receptor Agonist in Type 2 Diabetes With Early Dementia: A Multicenter, Randomized, Parallel-group, Double-blind, Placebo-controlled Trial
Asset
Mazdutide
Subcutaneous · GLP-1 / glucagon dual
Listed sites
8
Recruiting sites
6
Enrollment
420
estimated
Study population
Alzheimer's / cognition, Type 2 diabetes
Key I/E criteria
•BMI ≥20•HbA1c 7-9%
Primary endpoint
•Integrated Alzheimer's Disease Rating Scale (iADRS) Score Change
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. Type 2 diabetes mellitus (T2DM).
2. Aged 50-75 years (inclusive), male or female.
3. Early symptomatic dementia (Mild cognitive impairment or mild dementia), defined as:
1. MMSE score >20 and <27,
2. CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
3. Subjective memory complaints for ≥6 months.
4. Stable glycemic control regimen for ≥3 months prior to screening, meeting one of the following:
1. Lifestyle/dietary intervention alone (no glucose-lowering drugs),
2. Oral antidiabetic drugs (OADs), with or without once-daily basal insulin.
5. HbA1c 7.0-9.0% (inclusive) at screening.
6. BMI ≥20 kg/m², with stable weight (fluctuation <5%) for ≥3 months.
7. Stable treatment regimen for cognitive impairment for at least 3 months prior to screening and commit to its continuation throughout the study period, meeting one of the following criteria:
1. No treatment: Not receiving any pharmacological or non-pharmacological interventions for cognitive impairment;
2. Non-pharmacological therapy only: Engaged exclusively in non-drug interventions (e.g., cognitive training);
3. Pharmacological therapy: Using approved symptomatic cognitive-enhancing medications (e.g., cholinesterase inhibitors, NMDA receptor antagonists), excluding disease-modifying therapies for Alzheimer's disease (AD).
8. Ability to comply with systematic cognitive and functional assessments.
9. Fully understands the trial protocol, voluntarily signs the informed consent form (ICF), and agrees to adhere to all study requirements and restrictions.
Exclusion criteria
1. Evidence of other neurodegenerative diseases that may affect cognition, excluding Alzheimer's disease, including:
1. Frontotemporal dementia (FTD) and its variants
2. Parkinson's disease (PD), dementia with Lewy bodies (DLB)
3. Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD)
4. Multiple system atrophy (MSA), multiple sclerosis (MS), Huntington's disease (HD), etc.
2. Current diagnosis of a poorly controlled or unstable psychiatric disorder (including but not limited to schizophrenia, bipolar disorder, major depressive disorder, generalized anxiety disorder, personality disorders, etc.), which, in the investigator's judgment, may interfere with study assessments, affect treatment compliance, or increase participant risk.
3. With a Patient Health Questionnaire-9 (PHQ-9) score ≥10 at screening, or a Generalized Anxiety Disorder Scale-7 (GAD-7) score ≥10 at screening.
4. History of stroke (ischemic/hemorrhagic), transient ischemic attack (TIA), or epileptic seizure within 3 months prior to screening; Current or prior diagnosis of central nervous system (CNS) disorders that may impair cognitive function, including but not limited to:
CNS infections, Intracranial tumors, Metabolic encephalopathy, Neurological disorders due to malnutrition, or Severe traumatic brain injury.
5. Acute hyperglycemic/hypoglycemic events within 1 year, including: Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and Hypoglycemic coma
6. Use of GLP-1R agonists, GLP-1R/GIPR dual agonists, or GLP-1R/GCGR dual agonists within 3 months prior to screening.
7. Regular use (>2 doses/week) of moderate-to-strong anticholinergic drugs within 4 weeks prior to screening; Use within 3 months prior to screening of: Anti-Parkinsonian drugs, Antiepileptic drugs, Antipsychotics, Morphine and opioid analgesics (Exemption: Short-term use [<5 days] for surgery/acute injury, if completed >4 weeks before screening); Use within 4 weeks prior to screening of: CNS stimulants; Medical/recreational cannabis, cannabinoids, or cannabidiol (CBD).a. Moderate/high anticholinergics, antiparkinsonian/antiepileptic drugs.
8. Alcohol abuse (defined as >21 units/week for men or >14 units/week for women; 1 unit = 360 mL beer, 150 mL wine, or 45 mL spirits).
9. Medical history of:
1. Medullary thyroid carcinoma (MTC), pancreatitis
2. Multiple endocrine neoplasia type 2 (MEN2)
3. Gallbladder/biliary disease, severe gastrointestinal disorders, or bowel resection
4. Active malignancy
10. Uncontrolled or potentially unstable diabetic retinopathy/maculopathy.
11. Severe organ dysfunction, including:
1. ALT/AST >3× upper limit of normal (ULN)
2. eGFR <45 mL/min/1.73m² (CKD-EPI equation)
3. Unstable angina, myocardial infarction (MI), or NYHA Class II+ heart failure within 3 months
12. Known/suspected hypersensitivity to the investigational product or related compounds
13. Pregnancy, lactation, or women of childbearing potential not using highly effective contraception.
14. MRI contraindications (e.g., metal implants, claustrophobia).
15. Participation in other clinical trials within 3 months, involving an investigational medicinal product or enrollment in any other type of medical research judged not to be scientifically or medically compatible with this study.
16. Any other condition deemed by the investigator to compromise safety or interfere with study assessments.
Endpoints (22)
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
2 endpointsChange in Body Weight
Time frame:From Baseline to Week 12, 20, 28, 36, 44, 52, 60, 68 and 76.
Body weight, absolute change (kg)
change from baseline, improvement
Change in Body Mass Index (BMI)
Time frame:From Baseline to Week 12, 20, 28, 36, 44, 52, 60, 68 and 76.
BMI, change
change from baseline, improvement
Glycemic / diabetes
3 endpointsChange in Glycated Haemoglobin (HbA1c) Levels
Time frame:From Baseline to Week 28, 52 and 76
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Change in Fasting Plasma Glucose Levels
Time frame:From Baseline to Week 28, 52 and 76
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Change in 2-hour Postprandial Plasma Glucose Levels
Time frame:From Baseline to Week 52 and 76
Postprandial glucose
change from baseline, improvement
Safety / tolerability / PK
2 endpointsIncidence of Treatment-emergent Adverse Events
Time frame:From Baseline to Week 76
Treatment-emergent AEs (any)
event count, event
Incidence of Treatment-emergent Serious Adverse Events
Time frame:From Baseline to Week 76
Serious AEs (any)
event count, event
Other clinical outcomes
14 endpointsIntegrated Alzheimer's Disease Rating Scale (iADRS) Score Change
Time frame:From Baseline to Week 28, 52 and 76
change from baseline, improvement
Mini-Mental State Examination (MMSE) Score Change
Time frame:From Baseline to Week 28, 52 and 76
change from baseline, improvement
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Score Change
Time frame:From Baseline to Week 28, 52 and 76
change from baseline, improvement
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score Change
Time frame:From Baseline to Week 28, 52 and 76
change from baseline, improvement
Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Score Change
Time frame:From Baseline to Week 28, 52 and 76
change from baseline, improvement
Change in Total Brain Volume
Time frame:From Baseline to Week 76
change from baseline, descriptive
Change in Total White Matter Volume
Time frame:From Baseline to Week 76
change from baseline, descriptive
Change in Total Gray Matter Volume
Time frame:From Baseline to Week 76
change from baseline, descriptive
Change in Total White Matter Lesion Volume
Time frame:From Baseline to Week 76
change from baseline, improvement
Change in Cortical Gray Matter Lobar Volumes
Time frame:From Baseline to Week 76
change from baseline, descriptive
Change in Subcortical Nuclei Volumes
Time frame:From Baseline to Week 76
change from baseline, descriptive
Changes in MRI-derived Alzheimer's disease (AD) signature region volumes
Time frame:From Baseline to Week 76
change from baseline, descriptive
Changes in cortical thickness of AD-susceptible regions
Time frame:From Baseline to Week 76
change from baseline, improvement
Change in Amyloid-beta (Aβ) plaque deposition measured by Aβ-PET/MR
Time frame:From Baseline to Week 76
change from baseline, improvement
Other (unclassified)
1 endpointChange in Blood-Based Neurodegeneration Biomarkers
Time frame:From Baseline to Week 76
change from baseline, descriptive
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.