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

NCT07083154 | Recruiting Phase 3 DMC

• 1 other identifier: 2025-0502-01
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Dementia, Mild; Mild Cognitive Impairment; Type 2 Diabetes

Keywords

Type 2 Diabetes; Mild Dementia; Mild Cognitive Impairment; Dual GLP-1/Glucagon Receptor Agonist; Early-Stage Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

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

  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.

  From Baseline to Week 76

Secondary Outcomes (13)

• Mini-Mental State Examination (MMSE) Score Change

  From Baseline to Week 76

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

  From Baseline to Week 76

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

  From Baseline to Week 76

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

  From Baseline to Week 76

• Change in Total Brain Volume

  From Baseline to Week 76

Other Outcomes (8)

• Incidence of Treatment-emergent Adverse Events

  From Baseline to Week 76

• Incidence of Treatment-emergent Serious Adverse Events

  From Baseline to Week 76

• Change in Blood-based biomarkers related to AD pathology and neurodegeneration

  From Baseline to Week 76

Study Arms (2)

Mazdutide group

EXPERIMENTAL

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.

Drug: Mazdutide

Placebo group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

Matching placebo is administered once weekly by subcutaneous injection using a prefilled autoinjector pen. Participants will undergo the same blinded titration and dose-adjustment schedule as the mazdutide group, including corresponding 2.0 mg, 4.0 mg, and, where applicable, 6.0 mg dosing levels. Participants unable to tolerate a given dosing level may remain at the highest tolerated level. The total treatment duration is 76 weeks.

Placebo group

Mazdutide DRUG

Mazdutide is administered once weekly by subcutaneous injection using a prefilled autoinjector pen, preferably on the same day each week. Treatment is initiated at 2.0 mg once weekly and up-titrated to 4.0 mg once weekly during Weeks 4-12 according to individual tolerability. After at least 4 weeks at 4.0 mg, further escalation to 6.0 mg once weekly may be considered if prespecified criteria are met. Participants who are unable to tolerate a given dose may continue treatment at the highest tolerated dose. The total treatment duration is 76 weeks.

Also known as: IBI362

Mazdutide group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes according to the American Diabetes Association criteria;
• Aged 50-75 years (inclusive), male or female.
• Early-stage cognitive impairment (defined as mild cognitive impairment or mild dementia), with all of the following:
• MMSE score \>20 and \<27,
• CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
• A history of gradual and progressive cognitive decline for at least 6 months, reported by the participant or an informant.
• Stable glycemic control regimen for ≥3 months prior to screening, meeting one of the following:
• Lifestyle/dietary intervention alone (no glucose-lowering drugs),
• Oral antidiabetic drugs (OADs), with or without once-daily basal insulin.
• HbA1c 7.0-9.0% (inclusive) at screening.
• BMI ≥20 kg/m², with stable weight (fluctuation \<5%) for ≥3 months.
• 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:
• No treatment: Not receiving any pharmacological or non-pharmacological interventions for cognitive impairment;
• Non-pharmacological therapy only: Engaged exclusively in non-drug interventions (e.g., cognitive training);
• Pharmacological therapy: Using approved symptomatic cognitive-enhancing medications (e.g., cholinesterase inhibitors, NMDA receptor antagonists), excluding disease-modifying therapies for Alzheimer's disease (AD).

You may not qualify if:

• 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;
• 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.
• 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.
• 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;
• Acute hyperglycemic/hypoglycemic events within 1 year, including: Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and Hypoglycemic coma
• 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;
• 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.
• 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).
• Medical history of:
• Medullary thyroid carcinoma (MTC), pancreatitis
• Multiple endocrine neoplasia type 2 (MEN2)
• Gallbladder/biliary disease, severe gastrointestinal disorders, or bowel resection
• Active malignancy
• Uncontrolled or potentially unstable diabetic retinopathy/maculopathy.
• Severe organ dysfunction, including:

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead
• Nanjing First Hospital, Nanjing Medical University: collaborator
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Jiangsu Province Hospital of Traditional Chinese Medicine: collaborator
• Changzhou No.2 People's Hospital: collaborator
• Huadong Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• The Second Affiliated Hospital of Dalian Medical University: collaborator

Study Sites (8)

Department of Endocrinology, Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Department of Endocrinology, Changzhou No.2 People's Hospital

Changzhou, Jiangsu, China

RECRUITING

Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University

Nanjing, Jiangsu, 210000, China

RECRUITING

Department of Endocrinology, Endocrine and Metabolic Disease Medical Center,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

Nanjing, Jiangsu, 210008, China

RECRUITING

Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine

Nanjing, Jiangsu, China

RECRUITING

The Second Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

NOT YET RECRUITING

Department of Endocrinology, Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

Department of Endocrinology, Huadong Hospital Affiliated to Fudan University

Shanghai, 200040, China

RECRUITING

MeSH Terms

Conditions

Dementia; Lymphoma, Follicular; Cognitive Dysfunction; Diabetes Mellitus, Type 2

Interventions

mazdutide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cognition Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Yan Bi, MD, PhD

  Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Bi, MD, PhD

CONTACT

6-25-83-105302.; biyan@nju.edu.cn

Zhou Zhang, MD, PhD

CONTACT

86-25-83-105302; zhangzhou@smail.nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: July 24, 2025
• Study Start: September 27, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will become available after study completion and primary publication for 3 years.
• Access Criteria: Data requests require a valid research proposal and signed data use agreement. Approval is contingent on compliance with applicable laws and ethical guidelines.

Locations

CN (8)