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Trial · Interventional

RecruitingPhase 3Registry data

Mazdutide in Type 2 Diabetes With Early-Stage Cognitive Impairment (LIGHT-COG Study)

Overview

Status
Recruiting
Phase
Phase 3
Enrollment
420 participants (estimated)
Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Other
Design
Randomized · Quadruple masking
Countries
1 country

China

Start
27 Sept 2025
Primary completion
1 Aug 2029 (estimated)
Completion
1 Aug 2029 (estimated)
First posted
24 Jul 2025
Last update posted
2 Sept 2026
Conditions
Dementia, Mild · Mild Cognitive Impairment · Type 2 Diabetes

Timeline

1 trial · 1 ongoing

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202520262027202820292030
  1. Ph 3

    Mazdutide in Type 2 Diabetes With Early-Stage Cognitive Impairment (LIGHT-COG Study)

    NCT07083154

    27 Sept 2025 to est. 1 Aug 2029

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The LIGHT-COG study is a 76-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating the efficacy and safety of mazdutide in 420 participants with type 2 diabetes (T2D) and early-stage cognitive impairment, defined as mild cognitive impairment (MCI) or mild dementia. Participants are randomized 1:1 to receive once-weekly subcutaneous mazdutide, with dose escalation according to the protocol, or matching placebo, in addition to background glucose-lowering therapy. The primary objective is to determine whether 76 weeks of mazdutide treatment can slow cognitive and functional decline compared with placebo in this population.

Interventions

  • MazdutideDrug
  • PlaceboDrug

Arms2

  • Experimental

    Mazdutide group

    Participants will receive once-weekly subcutaneous mazdutide, starting at 2.0 mg and titrated to 4.0 mg, with optional escalation to 6.0 mg according to prespecified criteria. Participants unable to tolerate a given dose will remain on the highest tolerated dose, in addition to background glucose-lowering therapy.

  • Placebo comparator

    Placebo group

    Participants will receive weekly subcutaneous injections of matched placebo, in addition to their existing glucose-lowering therapy.

Primary outcomes1

Outcomes the sponsor listed as primary.

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

    Time frame · From Baseline to Week 76

    Registry description

    The change in Integrated Alzheimer's Disease Rating Scale (iADRS) scores from baseline to Week 76 will be compared between the treatment group and the placebo group to assess the drug's potential to improve or slow cognitive decline. iADRS is a composite endpoint that integrates cognitive and functional assessments (scores from Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) and Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living(ADCS-iADL)) to generate a total score (range: 0-144). The calculation formula is: iADRS score = (85 - ADAS-Cog13 score) + ADCS-iADL score A lower score indicates more severe cognitive and functional impairment.

Secondary outcomes(13)
  1. Mini-Mental State Examination (MMSE) Score Change

    Time frame · From Baseline to Week 76

    Registry description

    The change in Mini-Mental State Examination (MMSE) scores from baseline to Week 76 will be compared between the treatment group and the placebo group to assess the drug's potential to improve or slow cognitive decline. It assesses multiple cognitive domains, including orientation, memory, attention and calculation, recall ability, language, and visuospatial skills. The total score ranges from 0 to 30, with higher scores indicating better cognitive function.

  2. Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Score Change

    Time frame · From Baseline to Week 76

    Registry description

    The change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores from baseline to Week 76 will be compared between the treatment group and the placebo group to assess the drug's potential to improve or slow cognitive decline. The score ranges from 0 to 18, with higher scores indicating greater severity of cognitive and functional impairment.

  3. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score Change

    Time frame · From Baseline to Week 76

    Registry description

    The change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) scores from baseline to Week 76 will be compared between the treatment group and the placebo group to assess the drug's potential to improve or slow cognitive decline. The score ranges from 0 to 85, with higher scores indicating more significant cognitive impairment.

  4. Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Score Change

    Time frame · From Baseline to Week 76

    Registry description

    The change in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) scores from baseline to Week 76 will be compared between the treatment group and the placebo group to assess the drug's potential to improve or slow functional decline. The total score ranges from 0 to 59, with lower scores indicating more severe functional impairment.

  5. Change in Total Brain Volume

    Time frame · From Baseline to Week 76

    Registry description

    The change in total brain volume evaluated by structural MRI from baseline to Week 76 will be compared between the treatment group and the placebo group.

  6. Change in Total White Matter Lesion Volume

    Time frame · From Baseline to Week 76

    Registry description

    The change in total white matter lesion volume evaluated by sturctural MRI from baseline to Week 76 will be compared between the treatment group and the placebo group.

  7. Change in hippocampal volume

    Time frame · From Baseline to Week 76

    Registry description

    Change from baseline to Week 76 in hippocampal volume assessed by structural brain MRI.

  8. Change in entorhinal cortex volume

    Time frame · From Baseline to Week 76

    Registry description

    Change from baseline to Week 76 in entorhinal cortex volume assessed by structural brain MRI.

  9. Change in Body Weight

    Time frame · From Baseline to Week 76.

    Registry description

    Change in body weight from baseline to weeks 76.

  10. Change in Body Mass Index (BMI)

    Time frame · From Baseline to Week 76.

    Registry description

    Change in BMI from baseline to week 76.

  11. Change in Glycated Haemoglobin (HbA1c) Levels

    Time frame · From Baseline to Week 76

    Registry description

    Change in HbA1c levels from baseline to week 76

  12. Change in Fasting Plasma Glucose Levels

    Time frame · From Baseline to Week 76

    Registry description

    Change in fasting plasma glucose levels from baseline to week 76

  13. Change in 2-hour Postprandial Plasma Glucose Levels

    Time frame · From Baseline to Week 76

    Registry description

    Change in fasting plasma glucose levels from baseline to week 76

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 50 Years up to 75 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Diagnosis of type 2 diabetes according to the American Diabetes Association criteria; 2. Aged 50-75 years (inclusive), male or female. 3. Early-stage cognitive impairment (defined as mild cognitive impairment or mild dementia), with all of the following: 1. MMSE score \>20 and \<27, 2. CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5, 3. A history of gradual and progressive cognitive decline for at least 6 months, reported by the participant or an informant. 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. Known or suspected neurodegenerative disorders other than AD that are likely to be a major cause of cognitive impairment or to interfere with cognitive assessment, including but not limited to frontotemporal dementia and related syndromes, dementia with Lewy bodies, Parkinson's disease with cognitive impairment or dementia, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and Huntington's disease; 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. Ischaemic or haemorrhagic stroke, transient ischaemic attack, or epileptic seizure within 3 months before screening; or other current or clinically significant central nervous system disorders or injuries likely to impair cognitive function or interfere with cognitive assessment, including but not limited to central nervous system infection, intracranial tumour, multiple sclerosis, metabolic encephalopathy, neurological disorders related 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-1 receptor agonists, dual GIP/GLP-1 receptor agonists, dual GLP-1/glucagon receptor agonists, or triple GIP/GLP-1/glucagon receptor agonists within 3 months before 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. History of unstable angina or myocardial infarction within 3 months before screening, or current heart failure of NYHA class II or higher. 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.

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