LIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes

NCT05313529 | Active Not Recruiting

• 1 other identifier: 2022-LCYJ-ZD-03
• Study Type: interventional
• Target: 396
• Locations: 1 country
• Sites: 5

Brief Summary

This is an investigator-led prospective, randomized, open label, parallel study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the cognitive function in T2DM patients with mild cognitive impairment (MCI), consisting of a 48-week core study followed by a 28-week extension phase.

Conditions

Mild Cognitive Impairment; Type 2 Diabetes Mellitus

Keywords

Functional MRI; cognition; Olfactory function; Liraglutide, Empagliflozin and Linagliptin

Outcome Measures

Primary Outcomes (1)

• Mild cognitive impairment (MCI) remission rate

  MCI mitigation is defined by three criteria: an education-adjusted score of the Montreal Cognitive Assessment (MoCA) ≥26, no cognitive deficits in any explored cognitive subdomain, including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory, evaluated by Trail-Making Test, Stroop Color-Word Test and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively, and preservation of ability to perform instrumental activity of daily living (IADL) with a Functional Activities Questionnaire (FAQ) score \<5.

  The core study spans from baseline to 48 weeks

Secondary Outcomes (75)

• Change in score of Mini-Mental State Examination (MMSE)

  from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).

• Changes in score of MoCA

  from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).

• Changes in total score of RBANS

  from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).

• Change in the RBANS index score of immediate memory

  from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).

• Change in the RBANS index score of visuospatial/constructional

  from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase).

Study Arms (3)

Liraglutide

EXPERIMENTAL

Liraglutide will be titrated from 0.6mg/day to a final dose 1.8mg/day during the first 2 weeks, if well tolerated. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but liraglutide could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Liraglutide

Empagliflozin

EXPERIMENTAL

Empagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Empagliflozin

linagliptin

EXPERIMENTAL

linagliptin will be initiated at 5mg/ day every morning. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but linagliptin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Linagliptin

Interventions

Liraglutide DRUG

Liraglutide will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study

Also known as: metformin

Liraglutide

Empagliflozin DRUG

Empagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Empagliflozin

Linagliptin DRUG

Iinagliptin will be initiated at 5mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

linagliptin

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged ≥40 and ≤75 years, of any gender.
• Type 2 diabetes diagnosed according to the American Diabetes Association criteria
• Mild cognitive impairment diagnosed according to the established criteria
• Cognitive concern from the patient, or an informant or skilled clinicians
• Objective evidence of cognitive impairment: education-adjusted MoCA score ≤ 25 and ≥ 18; or ≥1.0 standard deviation below the mean of age- and education-specific groups on any cognitive subdomain
• Preservation of independence in daily living abilities: Barthel Index score ≥ 60
• Absence of dementia
• Treatment with a stable glucose lowering regimen of metformin monotherapy (≥ 1,000 mg daily) or combination with sulfonylurea/glibenclamide/glycosidase inhibitor/basal insulin over the previous 3 months
• Glycosylated hemoglobin (HbA1c) during screening between ≥7.0% and ≤10.0%
• BMI of ≥ 19 kg/m2
• Education duration of ≥6 years
• Right-handed participants
• Understanding of the research procedures and methods, potential benefits and risks of the trial, and sign written informed consent

You may not qualify if:

• History of other dementia-related neurological diseases, depression within the past 2 years, developmental disorders, mania, depression, schizophrenia, etc.
• Significant nasal sinusitis, nasal cavity and sinus polyps, cranial or nasopharyngeal tumors and other space-occupying lesions, congenital diseases and trauma of the nose, maxillofacial area, and skull base that affect olfaction. Symptoms of upper respiratory tract infection on the day of MRI examination, including nasal congestion, rhinorrhea, fever, etc.
• Acute metabolic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemic coma within the previous 6 months
• Severe organ dysfunction of heart, liver, kidneys, and thyroid, including unstable angina, myocardial infarction, or grade II and above cardiac insufficiency within 3 months before screening; estimated glomerular filtration rate (eGFR) by CKD-EPI formula \&lt;45 mL/min/1.73 m², alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater exceeding twice the upper limit of normal, hyperthyroidism or uncontrolled hypothyroidism
• History of medullary thyroid carcinoma, pancreatitis, multiple endocrine neoplasia syndrome type 2, recurrent urinary tract infections, severe gastrointestinal diseases or history of gastrointestinal surgery, history of malignant tumors
• With MRI contraindications, such as implanted metal prosthesis, claustrophobia, etc.
• Females who are pregnant, lactating, breast feeding or of child bearing age without effective contraception
• Participated in other clinical trials within the previous 6 months
• Known or suspected allergy to the study drugs
• Received treatment with GLP-1RAs, dual GLP-1R/GCGR agonist, SGLT-2 inhibitors or DPP4 inhibitors in the past 3 months
• Known history of drug or alcohol abuse within the past 6 months

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead
• Nanjing First Hospital, Nanjing Medical University: collaborator
• The Affiliated Jiangning Hospital of Nanjing Medical University: collaborator
• Wuxi People's Hospital: collaborator
• Changzhou No.2 People's Hospital: collaborator

Study Sites (5)

Department of Endocrinology, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University

Changzhou, Jiangsu, 213000, China

Location

Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University

Nanjing, Jiangsu, 210000, China

Location

Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Location

Department of Endocrinology, the Affiliated Jiangning Hospital of Nanjing Medical University

Nanjing, Jiangsu, 211100, China

Location

Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University

Wuxi, Jiangsu, 214000, China

Location

Related Publications (4)

• Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21.

  PMID: 31221697 RESULT

• Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2.

  PMID: 29500313 RESULT

• Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.

  PMID: 35263425 RESULT

• Yu C, Yang H, Zhang B, Chen S, Yang S, Li F, Zhu W, Zhai B, Wu T, Zhao S, Zhang W, Tong X, Duan Y, Zhang L, Chao Y, Wu J, Zhu X, Wang K, Ye X, Zhang X, Xu X, Cheng H, Liu J, Zhang J, Wang Y, Zhang Z, Yan W, Bi Y. Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase. BMJ Open. 2025 Aug 21;15(8):e095382. doi: 10.1136/bmjopen-2024-095382.

  PMID: 40840993 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cognitive Dysfunction

Interventions

Liraglutide; Metformin; empagliflozin; Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Officials

• Yan Bi, MD, PhD

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 19, 2022
• First Posted: April 6, 2022
• Study Start: October 8, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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 (5)