Actively Recruiting
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
Led by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Updated on 2026-03-05
420
Participants Needed
8
Research Sites
N/A
Total Duration
On this page
Sponsors
T
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Lead Sponsor
N
Nanjing First Hospital, Nanjing Medical University
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are investigating the potential effects of mazdutide, a GLP-1/GCG dual receptor agonist, on cognitive dysfunction in people with type 2 diabetes and early dementia. This 76-week, multicenter, randomized, double-blind, placebo-controlled study will compare mazdutide against a placebo to evaluate whether it can modify disease progression. The trial aims to assess cognitive improvement alongside changes in brain structure, metabolic health, neurodegenerative biomarkers, and safety outcomes. Participants are randomly assigned to receive either weekly subcutaneous injections of mazdutide or a matched placebo, in addition to their current glucose-lowering treatments. The mazdutide dose starts at 2.0 mg weekly and is gradually increased to a maintenance dose of 4.0 mg, with an optional increase to 6.0 mg if needed and tolerated. If blood sugar control remains poor despite treatment, rescue therapies such as insulin glargine, metformin, or other medications may be added based on the investigator's judgment. The treatment phase lasts 76 weeks. During the study, participants will undergo detailed cognitive and metabolic assessments at the start and at weeks 28, 52, and 76. Safety visits occur at week 4 and every 8 weeks thereafter to monitor side effects, adherence, and metabolic status. Advanced brain imaging and blood biomarker tests will be conducted to track changes in brain volume, amyloid plaque deposition, and neurodegeneration. The main outcome measured is the change in the Integrated Alzheimer's Disease Rating Scale score over time, along with several secondary cognitive and metabolic measures.
CONDITIONS
Brief Title
GLP-1/GCG Dual Agonist in Type 2 Diabetes With Early Dementia (LIGHT-COG Study)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Have a diagnosis of type 2 diabetes mellitus.
- Be between 50 and 75 years old, male or female.
- Have early symptomatic dementia defined by: MMSE score greater than 20 and less than 27, CDR global score between 0.5 and 1.0 inclusive with a memory subscore of at least 0.5, and subjective memory complaints lasting 6 months or more.
- Have had a stable blood sugar control regimen for at least 3 months before screening, including either lifestyle changes alone or oral antidiabetic drugs with or without once-daily basal insulin.
- Have HbA1c levels between 7.0% and 9.0% at screening.
- Have a body mass index (BMI) of 20 kg/m² or higher with stable weight (fluctuations less than 5%) for at least 3 months.
- Have been on a stable treatment regimen for cognitive impairment for at least 3 months prior to screening and agree to continue this during the study, which may include no treatment, non-drug therapies, or approved symptomatic medications excluding disease-modifying Alzheimer's treatments.
- Be able to comply with cognitive and functional assessments.
- Understand the trial protocol, voluntarily sign informed consent, and agree to follow all study requirements.
You will not qualify if you...
- Have other neurodegenerative diseases affecting cognition besides Alzheimer's disease, such as frontotemporal dementia, Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, multiple sclerosis, or Huntington's disease.
- Have an unstable or poorly controlled psychiatric disorder that may interfere with the study.
- Have a PHQ-9 score of 10 or higher, or a GAD-7 score of 10 or higher at screening.
- Have had a stroke, transient ischemic attack, or epileptic seizure within 3 months prior to screening, or other central nervous system disorders that impair cognition.
- Have experienced acute severe blood sugar events like diabetic ketoacidosis or hypoglycemic coma within the past year.
- Have used GLP-1 receptor agonists or similar drugs within 3 months before screening.
- Regularly use moderate-to-strong anticholinergic drugs, anti-Parkinsonian drugs, antiepileptic drugs, antipsychotics, morphine/opioids, CNS stimulants, or cannabis-related products within specified timeframes before screening.
- Have alcohol abuse defined as more than 21 units per week for men or more than 14 units per week for women.
- Have medical histories including medullary thyroid carcinoma, pancreatitis, multiple endocrine neoplasia type 2, gallbladder or biliary disease, severe gastrointestinal disorders, active malignancy.
- Have uncontrolled or unstable diabetic retinopathy or maculopathy.
- Have severe organ dysfunction including liver enzymes above three times normal, low kidney function (eGFR below 45), recent unstable heart conditions.
- Have known allergies to the study drug or related compounds.
- Are pregnant, breastfeeding, or women of childbearing potential not using effective contraception.
- Have MRI contraindications such as metal implants or severe claustrophobia.
- Participate in other clinical trials within 3 months that might interfere with this study.
- Have any other condition that the investigator considers unsafe or interfering with study assessments.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 76 weeks
Participants receive weekly subcutaneous injections of the study drug or placebo with dose escalation over 4 to 12 weeks to reach a target dose, continuing for a total of 76 weeks. During this time, participants undergo comprehensive cognitive and metabolic assessments, as well as safety monitoring visits.
1 baseline visit, safety visits at Week 4 and every 8 weeks thereafter, and comprehensive evaluations at Weeks 28, 52, and 76
Trial Site Locations
Total: 8 locations
1
Department of Endocrinology, Xiangya Hospital of Central South University
Changsha, Hunan, China, 410008
Not Yet Recruiting
2
Department of Endocrinology, Changzhou No.2 People's Hospital
Changzhou, Jiangsu, China
Actively Recruiting
3
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University
Nanjing, Jiangsu, China, 210000
Actively Recruiting
4
Department of Endocrinology, Endocrine and Metabolic Disease Medical Center,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
Nanjing, Jiangsu, China, 210008
Actively Recruiting
5
Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine
Nanjing, Jiangsu, China
Actively Recruiting
6
The Second Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, China
Not Yet Recruiting
7
Department of Endocrinology, Shanghai General Hospital
Shanghai, Shanghai Municipality, China, 200080
Actively Recruiting
8
Department of Endocrinology, Huadong Hospital Affiliated to Fudan University
Shanghai, China, 200040
Actively Recruiting
Research Team
Y
Yan Bi, MD, PhD
Z
Zhou Zhang, MD, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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