GLP-1/GCG dual agonist (mazdutide) for people with type 2 diabetes and early dementia
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
This study will test whether weekly injections of mazdutide can help thinking and memory in people aged 50–75 who have type 2 diabetes and early dementia.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 420 (estimated) |
| Ages | 50 Years to 75 Years |
| Sex | All |
| Sponsor | The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School Academic / other |
| Locations | 8 sites (Changsha, Hunan and 7 other locations) |
| Trial ID | NCT07083154 on ClinicalTrials.gov |
What this trial studies
This is a 76-week, multicenter, randomized, double-blind, placebo-controlled trial enrolling 420 people with type 2 diabetes and early symptomatic dementia. Participants are randomized 1:1 to weekly subcutaneous mazdutide with stepwise dose escalation (target maintenance 4.0 mg, optional increase to 6.0 mg if tolerated) or matched placebo while continuing their usual glucose-lowering therapy. The primary outcome is change in cognitive function, with key secondary outcomes including brain imaging, neurodegenerative biomarkers, metabolic measures, and safety. Participants undergo baseline cognitive and metabolic assessments, safety visits at Week 4 and every 8 weeks, and comprehensive evaluations including imaging at Weeks 28, 52, and 76.
Who should consider this trial
Good fit: Ideal candidates are people aged 50–75 with type 2 diabetes and early symptomatic dementia or mild cognitive impairment (MMSE >20 and <27, CDR global 0.5–1.0 with memory impairment), HbA1c 7.0–9.0%, BMI ≥20 kg/m², and a stable glucose and cognitive treatment regimen for at least 3 months.
Not a fit: People with more advanced dementia, outside the age or HbA1c/BMI ranges, unstable glucose control or treatment regimens, or major uncontrolled comorbidities are unlikely to benefit from this specific protocol.
Why it matters
Potential benefit: If successful, mazdutide could slow or improve cognitive decline and also improve metabolic control in people with type 2 diabetes and early dementia.
How similar studies have performed: Some GLP-1 receptor agonists have shown promising signals for neuroprotection in early trials and observational studies, but GLP-1/GCG dual agonists like mazdutide are newer and lack definitive phase 3 evidence in dementia.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Type 2 diabetes mellitus (T2DM).
2. Aged 50-75 years (inclusive), male or female.
3. Early symptomatic dementia (Mild cognitive impairment or mild dementia), defined as:
1. MMSE score \>20 and \<27,
2. CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
3. Subjective memory complaints for ≥6 months.
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. Evidence of other neurodegenerative diseases that may affect cognition, excluding Alzheimer's disease, including:
1. Frontotemporal dementia (FTD) and its variants
2. Parkinson's disease (PD), dementia with Lewy bodies (DLB)
3. Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD)
4. Multiple system atrophy (MSA), multiple sclerosis (MS), Huntington's disease (HD), etc.
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. 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.
5. Acute hyperglycemic/hypoglycemic events within 1 year, including: Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and Hypoglycemic coma
6. Use of GLP-1R agonists, GLP-1R/GIPR dual agonists, or GLP-1R/GCGR dual agonists within 3 months prior to 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. Unstable angina, myocardial infarction (MI), or NYHA Class II+ heart failure within 3 months
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.
Where this trial is running
Changsha, Hunan and 7 other locations
- Department of Endocrinology, Xiangya Hospital of Central South University — Changsha, Hunan, 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, China (Recruiting)
- Department of Endocrinology, Endocrine and Metabolic Disease Medical Center,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University — Nanjing, Jiangsu, 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, China (Recruiting)
- Department of Endocrinology, Huadong Hospital Affiliated to Fudan University — Shanghai, China (Recruiting)
Study contacts
- Principal investigator: Yan Bi, MD, PhD — Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
- Study coordinator: Yan Bi, MD, PhD
- Email: biyan@nju.edu.cn
- Phone: 6-25-83-105302.
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.