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

Mild cognitive impairment (MCI) remission rate

Time frame · The core study spans from baseline to 48 weeks

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.

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

Time frame · 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).

The MMSE contains a total of 30 items that assess orientation, registration, attention and calculation, recall, and language, with a score range from 0 to 30. Generally, a higher MMSE score reflects a better cognitive function.

Changes in score of MoCA

Time frame · 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).

The MoCA (Chinese version) is a screening instrument for MCI comprised of 30 items to assess multiple cognitive domains (memory recall, visuospatial abilities, executive functions, attention, language, and orientation to time and place; scores range from 0 to 30, with higher scores indicating better cognitive function). Participants received one additional point if they had a MoCA score \< 30 and 12 years or less of formal school education.

Changes in total score of RBANS

Time frame · 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).

The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data, which consists of 12 task tests assessing 5 cognitive domains, namely immediate memory, visuospatial/ constructional, language, attention and delayed memory, with a score range from 40 to 160. A higher RBANS score reflects a better global cognitive function.

Change in the RBANS index score of immediate memory

Time frame · 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).

The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data. The RBANS includes 12 sub-tests that generate five age-adjusted index scores and a total score. The five indices include immediate memory (consisting of list learning and story memory tests), visuospatial/constructional domain (consisting of figure copying and line orientation tests), language (consisting of picture naming and semantic fluency tests), attention (consisting of digit span and coding tests) and delayed memory (consisting of list recall, story recall, figure recall and list recognition tests). Generally, a higher index score reflects a better cognitive subdomain function.

Change in the RBANS index score of visuospatial/constructional

Time frame · 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).

Measurements and instruments are the same as the RBANS index score of immediate memory.

Change in the RBANS index score of language

Time frame · 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).

Measurements and instruments are the same as the RBANS index score of immediate memory.

Change in the RBANS index score of attention

Time frame · 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).

Measurements and instruments are the same as the RBANS index score of immediate memory.

Change in the RBANS index score of delayed memory

Time frame · 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).

Measurements and instruments are the same as the RBANS index score of immediate memory.

Change in aggregate time to test completion for Trail Making Test (TMT)

Time frame · 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).

The TMT is a validated timed measure of processing speed, which consists of part A and part B (TMT-A and TMT-B). The time limits for performing the TMT-A and TMT-B are 180 and 300 seconds, respectively. Processing speed is estimated by the aggregate time in seconds to complete TMT-A and TMT-B such that less time indicate faster processing speed.

Change in aggregate time to test completion for Victoria Stroop Color-Word Test

Time frame · 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).

The Victoria Stroop Color-Word Test is a well-known measure of executive function. There are three indices including Stroop-dot, Stroop-word and Stroop-color word in the test. The color task consists of colored dots; the word task comprises ordinary words that are unrelated to the meaning of color; the color-word task consists of words written in color that indicate the meaning of the color, but the color of these words differs from the meaning of the word itself. The participants were asked to quickly read the color of the dots or Chinese words on the cards. The sum of consuming time taken to read the three cards is used as an index of executive function performance. Less time indicates better executive function.