NCT07485062

Exercise and Diabetes Interventions to Improve Brain Health in Older Adults With Type 2 Diabetes

Metabolic Optimization and Training InterVentions for Aging and Type 2 Diabetes to Enhance Cognition: the MOTIVATE Study

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 164 (estimated)
• Sponsor: Western University, Canada · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

Type 2 diabetes and low levels of physical activity are associated with an increased risk of cognitive decline in older adults. Improving blood sugar control and engaging in regular exercise may help support brain health and physical function in this population. The MOTIVATE study is a randomized clinical trial designed to examine the effects of supervised exercise and diabetes treatment with semaglutide, alone or in combination, on cognitive function, physical health, and brain-related outcomes in older adults with Type 2 diabetes. Participants will be assigned to one of four study groups involving exercise training, control exercise, semaglutide treatment, or standard diabetes care. Participants will complete supervised exercise sessions three times per week for 32 weeks, with some participants also receiving weekly semaglutide injections for 16 weeks. Assessments will include cognitive testing, physical and functional measures, blood-based metabolic markers, and brain imaging. This study aims to improve understanding of how exercise and diabetes treatments may support brain health in older adults with Type 2 diabetes.

Detailed description

Type 2 diabetes (T2D) and lack of engagement in physical activity are common in Canada, significantly increasing the risk of dementia among older adults. High blood sugar levels in people living with T2D are linked to poorer cognitive performance and faster cognitive decline. Even those at risk for T2D, due to slightly elevated blood sugar levels or being overweight, show signs of cognitive decline and brain abnormalities. Studies show that improving blood sugar control, losing weight, and engaging in physical activity can enhance cognitive function in long-term and spatial memory and decision-making. Semaglutide is primarily used to lower blood sugar levels, while resistance exercise is known to improve brain health and physical fitness. Thus, short-term pharmacotherapy in adjunct to RE may serve as a powerful therapy for older adults with T2D to achieve and sustain clinically relevant improvements in cognitive function and glycemic control, and to facilitate a healthier lifestyle. The present trial is a 32-week, real-world, randomized, open-label waitlist-controlled trial designed to show improvements in cognitive function and compare the effect of injectable semaglutide once-weekly versus standard of care as a short-term (16-weeks) adjunct to resistance exercise (RE) (32 weeks) versus its active control (balance-and-tone training (BAT)) in older adults with T2D. Participants will be randomly put into one of four groups: 1) drug and exercise, 2) no drug and exercise, 3) standard of care and non- intense exercise, or 4) standard of care and non-intense exercise. Exercise will be conducted in classes involving either resistance exercise (weighted movements using exercise machines) or an active control, balance and tone exercise (stretching and core). Cognitive function will be assessed using tasks of memory, learning, flexibility, and processing of information. Brain structure and function will be examined through magnetic resonance imaging (MRI) scans. Blood samples will be analyzed for markers of brain health and inflammation. After randomization, all outcome assessors will remain blinded to the study drug and exercise groups.

Conditions

• Type 2 Diabetes
• Cognitive Decline in Older Adults

Interventions

Type	Name	Description
DRUG	semaglutide	Injectable semaglutide administered once weekly by subcutaneous injection for 16 weeks, as prescribed and monitored by the study physician.
BEHAVIORAL	Moderate-Intensity Resistance Exercise	Supervised moderate-intensity resistance exercise training performed three times per week for 32 weeks.
BEHAVIORAL	Balance and Tone (BAT) Exercise	Supervised balance-and-tone (BAT) exercise performed three times per week for 32 weeks, serving as an active control exercise condition.

Timeline

• Start date: 2026-05-01
• Primary completion: 2029-05-01
• Completion: 2029-05-01
• First posted: 2026-03-20
• Last updated: 2026-03-20

Locations

1 site across 1 country: Canada