Effects of Mazdutide on Cognitive Function in Patients With Type 2 Diabetes and Early-Stage Cognitive Impairment: A Multicenter, Randomized, Parallel-group, Double-blind, Placebo-controlled Trial
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.
• Diagnosis of type 2 diabetes according to the American Diabetes Association criteria;
• Aged 50-75 years (inclusive), male or female.
• Early-stage cognitive impairment (defined as mild cognitive impairment or mild dementia), with all of the following:
‣ MMSE score \>20 and \<27,
⁃ CDR global score 0.5-1.0 (inclusive), with a CDR memory subscore ≥0.5,
⁃ A history of gradual and progressive cognitive decline for at least 6 months, reported by the participant or an informant.
• Stable glycemic control regimen for ≥3 months prior to screening, meeting one of the following:
‣ Lifestyle/dietary intervention alone (no glucose-lowering drugs),
⁃ Oral antidiabetic drugs (OADs), with or without once-daily basal insulin.
• HbA1c 7.0-9.0% (inclusive) at screening.
• BMI ≥20 kg/m², with stable weight (fluctuation \<5%) for ≥3 months.
• 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:
‣ No treatment: Not receiving any pharmacological or non-pharmacological interventions for cognitive impairment;
⁃ Non-pharmacological therapy only: Engaged exclusively in non-drug interventions (e.g., cognitive training);
⁃ Pharmacological therapy: Using approved symptomatic cognitive-enhancing medications (e.g., cholinesterase inhibitors, NMDA receptor antagonists), excluding disease-modifying therapies for Alzheimer's disease (AD).
• Ability to comply with systematic cognitive and functional assessments.
• Fully understands the trial protocol, voluntarily signs the informed consent form (ICF), and agrees to adhere to all study requirements and restrictions.