GLP-1/GCG Dual Agonist in Type 2 Diabetes With Early Dementia (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. A total of 420 type 2 diabetes patients with early dementia are randomized 1:1 to either the active treatment group (receiving subcutaneous injections of mazdutide weekly, with stepwise dose escalation to a maintenance dose per protocol) or the placebo group (receiving matched placebo injections). The primary objective is to evaluate the potential disease-modifying effects of mazdutide on cognitive dysfunction in type 2 diabetes.

Conditions

Dementia, Mild; Mild Cognitive Impairment; Type 2 Diabetes

Keywords

Type 2 Diabetes; Mild Dementia; Mild Cognitive Impairment; GLP-1/GCG Dual Agonist; Cognitive Dysfunction; Early Dementia

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 28, 52, and 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 28, 52 and 76

Secondary Outcomes (19)

• Mini-Mental State Examination (MMSE) Score Change

  From Baseline to Week 28, 52 and 76

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

  From Baseline to Week 28, 52 and 76

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

  From Baseline to Week 28, 52 and 76

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

  From Baseline to Week 28, 52 and 76

• Change in Total Brain Volume

  From Baseline to Week 76

Other Outcomes (2)

• Incidence of Treatment-emergent Adverse Events

  From Baseline to Week 76

• Incidence of Treatment-emergent Serious Adverse Events

  From Baseline to Week 76

Study Arms (2)

Mazdutide group

EXPERIMENTAL

Participants will receive weekly subcutaneous injections of mazdutide (starting at 2.0 mg, with stepwise dose escalation to a target maintenance dose of 4.0 mg and optional adaptive increase to 6.0 mg if necessary and tolerated) , in addition to their existing 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

Mazdutide DRUG

Mazdutide injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week. The starting dose is 2.0 mg administered once weekly (QW). Based on individual patient tolerance, the dose should be gradually increased to the target therapeutic dose of 4.0 mg QW over a period of 4 to 12 weeks. The protocol permits adaptive dose escalation up to 6.0 mg weekly when clinically indicated. For participants unable to tolerate dose increases, treatment continue at their maximum tolerated dose. The total intervention duration is 76 weeks.

Also known as: IBI362

Mazdutide group

Placebo DRUG

Placebo injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week. The starting dose is 2.0 mg administered once weekly (QW). Based on individual patient tolerance, the dose should be gradually increased to the target therapeutic dose of 4.0 mg QW over a period of 4 to 12 weeks. The protocol permits adaptive dose escalation up to 6.0 mg weekly when clinically indicated. For participants unable to tolerate dose increases, treatment continue at their maximum tolerated dose. The total intervention duration is 76 weeks.

Placebo 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:

• Type 2 diabetes mellitus (T2DM).
• Aged 50-75 years (inclusive), male or female.
• Early symptomatic dementia (Mild cognitive impairment or mild dementia), defined as:
• MMSE score \>20 and \<27,
• CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
• Subjective memory complaints for ≥6 months.
• 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:

• Evidence of other neurodegenerative diseases that may affect cognition, excluding Alzheimer's disease, including:
• Frontotemporal dementia (FTD) and its variants
• Parkinson's disease (PD), dementia with Lewy bodies (DLB)
• Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD)
• Multiple system atrophy (MSA), multiple sclerosis (MS), Huntington's disease (HD), etc.
• 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.
• 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.
• Acute hyperglycemic/hypoglycemic events within 1 year, including: Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and Hypoglycemic coma
• Use of GLP-1R agonists, GLP-1R/GIPR dual agonists, or GLP-1R/GCGR dual agonists within 3 months prior to 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

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
• Xiangya Hospital of Central South University: collaborator
• Jiangsu Province Hospital of Traditional Chinese Medicine: collaborator
• Changzhou No.2 People's Hospital: collaborator
• The Second Affiliated Hospital of Dalian Medical University: collaborator
• Huadong Hospital: 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: March 5, 2026

Record last verified: 2026-03

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)