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.
Type 2 diabetes mellitus (T2DM).
Aged 50-75 years (inclusive), male or female.
MMSE score >20 and <27,
CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
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.
Parallel
Mazdutide
DrugMazdutide 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
DrugPlacebo 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.
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.
Mini-Mental State Examination (MMSE) Score Change
The change in Mini-Mental State Examination (MMSE) 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. 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.
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Score Change
The change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) 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. The score ranges from 0 to 18, with higher scores indicating greater severity of cognitive and functional impairment.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score Change
The change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) 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. The score ranges from 0 to 85, with higher scores indicating more significant cognitive impairment.
Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) Score Change
The change in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL) 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 functional decline. The total score ranges from 0 to 59, with lower scores indicating more severe functional impairment.
Incidence of Treatment-emergent Adverse Events
Difference in incidence of treatment-emergent adverse events during the trial period (treatment vs. placebo).
Incidence of Treatment-emergent Serious Adverse Events
Difference in incidence of serious adverse events during the trial period (treatment vs. placebo).
Click on the lead sponsor to view all of their trials.
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Lead sponsor
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
Huadong Hospital
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
