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.

INTRODUCTION

Diabetes is a significant modifiable risk factor for cognitive dysfunction. There are currently no effective treatments that delay or reverse the progression of cognitive dysfunction. Accumulating evidence demonstrates that specific antidiabetes medications hold promise in improving cognitive function. However, the comparative effects of various antidiabetic drug classes on cognitive protection remain to be fully elucidated. This study aims to investigate and compare the cognitive benefits of liraglutide, empagliflozin and linagliptin on achieving mild cognitive impairment (MCI) remission in individuals with type 2 diabetes (T2D).

METHODS AND ANALYSIS

The LIGHT-MCI trial is an investigator-initiated, multicentre, open-label, parallel-group, randomised, superiority trial involving T2D patients with MCI, consisting of a 48-week core study followed by an extension phase through to 76 weeks. A total of 396 participants will be randomly allocated 1:1:1 to receive liraglutide, empagliflozin or linagliptin treatment. The primary outcome measure is the efficacy difference of liraglutide, empagliflozin and linagliptin in achieving MCI remission in individuals with T2D. The key secondary outcome measures include changes in scores of general cognition and various cognitive subdomains (including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory), basic and instrumental daily living ability, MRI-derived normalised measures of total brain volume, cerebral microstructures, cortical and nuclear volume, white matter hyperintensity, volume, white matter microstructural integrity, odour-induced brain activation and resting-state functional connectivity, olfactory function and metabolic parameters.

ETHICS AND DISSEMINATION

The LIGHT-MCI trial has received approval from the Ethics Committees of the Drum Tower Hospital Affiliated to Nanjing University Medical School (2022-092-02) and other participating centres in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation for Good Clinical Practice (ICH GCP E6). Informed consent is required for participation. Findings from this trial are disseminated through peer-reviewed publications, conference presentations, newsletters and social media.

TRIAL REGISTRATION NUMBER

NCT05313529.