NCT07083154

GLP-1/GCG Dual Agonist in Type 2 Diabetes With Early Dementia (LIGHT-COG Study)

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 420 (estimated)
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Academic / Other
• Sex: All
• Age: 50 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The LIGHT-COG study is a 76-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial investigating the potential disease-modifying effects of the GLP-1/GCG dual receptor agonist mazdutide on cognitive dysfunction in 420 patients with type 2 diabetes (T2D) and early dementia. Participants will be randomized 1:1 to receive either weekly subcutaneous injections of mazdutide (starting at 2.0 mg, with stepwise dose escalation to a target maintenance dose of 4.0 mg and optional adaptive increase to 6.0 mg if necessary and tolerated) or matched placebo, in addition to their existing glucose-lowering therapy. The primary objective is to assess cognitive improvement, with key secondary endpoints including brain structure and function alterations, metabolic improvement, neurodegenerative biomarkers, and safety outcomes. Participants will undergo comprehensive cognitive and metabolic assessments at baseline, followed by safety visits at Week 4 and every 8 weeks thereafter for monitoring of adverse events, adherence, and metabolic parameters. Comprehensive evaluations at Weeks 28, 52, and 76 will include cognitive assessments, advanced neuroimaging, and metabolic profiling. During the study period, if a subject's study drug has been titrated to the maximum tolerated dose or the maximum protocol-specified dose (6 mg), and glycemic control remains suboptimal (fasting venous blood glucose or fingertip capillary blood glucose \> 8.5 mmol/L on two consecutive measurements) during follow-up, individualized rescue therapy may be initiated upon the investigator's judgment. The choice of rescue regimen should be based on the investigator's comprehensive assessment of the subject's specific condition, including but not limited to glycemic levels, complications, hepatic and renal function, and risk of hypoglycemia. Optional rescue medications include insulin glargine, metformin, gliclazide modified-release, and acarbose. The investigator shall closely monitor the response to rescue therapy. The study should be terminated if any of the following occurs: inadequate glycemic control after rescue therapy, intolerance to rescue medications, or any other situation necessitating withdrawal as judged by the investigator. All decision-making basis, selection of rescue regimen, and efficacy evaluations must be thoroughly documented.

Conditions

• Dementia, Mild
• Mild Cognitive Impairment
• Type 2 Diabetes

Interventions

Type	Name	Description
DRUG	Mazdutide	Mazdutide 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.
DRUG	Placebo	Placebo 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.

Timeline

• Start date: 2025-09-27
• Primary completion: 2029-08-01
• Completion: 2029-08-01
• First posted: 2025-07-24
• Last updated: 2026-03-05

Locations

8 sites across 1 country: China