← Trials/Trial dossier/NCT07083154

RecruitingPhase 3

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 ≥20HbA1c 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

NCT IDNCT07083154
Org study ID2025-0502-01

Timeline

Milestones

Study first posted2025-07-24actual
Study start2025-09-27actual
Last update posted2026-03-05actual
Primary completion2029-08-01estimated
Study completion2029-08-01estimated

Assets

Investigational agents

Study populations

Who this study enrolls

Alzheimer's / cognitionType 2 diabetes

Eligibility

Who can enroll

Minimum age50 Years
Maximum age75 Years
SexAll
Healthy volunteersNot accepted

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

Other clinical outcomes
14
Glycemic / diabetes
3
Weight & body composition
2
Safety / tolerability / PK
2
Other (unclassified)
1

Weight & body composition

2 endpoints
Secondary/protocol endpoint

Change 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

Secondary/protocol endpoint

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 endpoints
Secondary/protocol endpoint

Change in Glycated Haemoglobin (HbA1c) Levels

Time frame:From Baseline to Week 28, 52 and 76

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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 endpoints
Other/protocol endpoint

Incidence of Treatment-emergent Adverse Events

Time frame:From Baseline to Week 76

Treatment-emergent AEs (any)

event count, event

Other/protocol endpoint

Incidence of Treatment-emergent Serious Adverse Events

Time frame:From Baseline to Week 76

Serious AEs (any)

event count, event

Other clinical outcomes

14 endpoints
Primary/protocol endpoint/low confidence

Integrated Alzheimer's Disease Rating Scale (iADRS) Score Change

Time frame:From Baseline to Week 28, 52 and 76

change from baseline, improvement

Secondary/protocol endpoint

Mini-Mental State Examination (MMSE) Score Change

Time frame:From Baseline to Week 28, 52 and 76

change from baseline, improvement

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

Change in Total Brain Volume

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint

Change in Total White Matter Volume

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint

Change in Total Gray Matter Volume

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint

Change in Total White Matter Lesion Volume

Time frame:From Baseline to Week 76

change from baseline, improvement

Secondary/protocol endpoint

Change in Cortical Gray Matter Lobar Volumes

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in Subcortical Nuclei Volumes

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint

Changes in MRI-derived Alzheimer's disease (AD) signature region volumes

Time frame:From Baseline to Week 76

change from baseline, descriptive

Secondary/protocol endpoint

Changes in cortical thickness of AD-susceptible regions

Time frame:From Baseline to Week 76

change from baseline, improvement

Secondary/protocol endpoint/low confidence

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 endpoint
Secondary/protocol endpoint/low confidence

Change in Blood-Based Neurodegeneration Biomarkers

Time frame:From Baseline to Week 76

change from baseline, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

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.