Clinical trial

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

Recruiting now · Phase 3 · 1 countries · Registry ID NCT07083154

Recruiting nowPhase 3Interventional

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age50 Years to 75 Years
SexAll
Healthy volunteersNot accepted
ConditionDementia, Mild, Mild Cognitive Impairment, Type 2 Diabetes

Full registry criteria

Inclusion Criteria: 1. Diagnosis of type 2 diabetes according to the American Diabetes Association criteria; 2. Aged 50-75 years (inclusive), male or female. 3. Early-stage cognitive impairment (defined as mild cognitive impairment or mild dementia), with all of the following: 1. MMSE score \>20 and \<27, 2. CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5, 3. A history of gradual and progressive cognitive decline for at least 6 months, reported by the participant or an informant. 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. 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; 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. 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; 5. Acute hyperglycemic/hypoglycemic events within 1 year, including: Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and Hypoglycemic coma 6. 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; 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. History of unstable angina or myocardial infarction within 3 months before screening, or current heart failure of NYHA class II or higher. 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.

Treatments and study arms

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.

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.

Primary outcomes

Integrated Alzheimer's Disease Rating Scale (iADRS) Score ChangeFrom Baseline to Week 76

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.

Study locations

8 locations were listed when this page was built. The first 40 are shown.

Department of Endocrinology, Xiangya Hospital of Central South University🇨🇳 Changsha, Hunan, China
Jing Wu, MD, PhDContact
Jing Wu, MD, PhDPrincipal Investigator
Department of Endocrinology, Changzhou No.2 People's Hospital🇨🇳 Changzhou, Jiangsu, China
Huijie Yang, MDContact
Xinhua Ye, MD, PhDPrincipal Investigator
Huijie Yang, MDSub Investigator
The Second Affiliated Hospital of Dalian Medical University🇨🇳 Dalian, Liaoning, China
Haixia Liu, MD, PhDContact
Haixia Liu, MD, PhDPrincipal Investigator
Department of Endocrinology, Endocrine and Metabolic Disease Medical Center,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University🇨🇳 Nanjing, Jiangsu, China
Yan Bi, MD, PhDContact
Zhou Zhang, MD, PhDContact
Yan Bi, MD, PhDPrincipal Investigator
Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine🇨🇳 Nanjing, Jiangsu, China
Yueting Zhao, MDContact
Yueting Zhao, MDPrincipal Investigator
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University🇨🇳 Nanjing, Jiangsu, China
Jindan Wu, MD, PhDContact
Jindan Wu, MD, PhDPrincipal Investigator
Peng Zhang, MDSub Investigator
Department of Endocrinology, Huadong Hospital Affiliated to Fudan University🇨🇳 Shanghai, China
Bin Lu, MD, PhDContact
Bin Lu, MD, PhDPrincipal Investigator
Cuiping Jiang, MDSub Investigator
Department of Endocrinology, Shanghai General Hospital🇨🇳 Shanghai, Shanghai Municipality, China
Fang Fang, MD, PhDContact
Fang Fang, MD,PhDPrincipal Investigator