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

What Was Tested

This registered phase 4 trial tested Semaglutide.

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.

It had four arms (groups): Resistance Exercise + Semaglutide (experimental), Standard of Care + Resistance Exercise (active comparator), Semaglutide + Balance and Tone Exercise (active comparator) and Standard of Care + Balance and Tone Exercise (active comparator).

Participants assigned to this arm will receive injectable semaglutide once weekly for 16 weeks, in addition to participating in supervised moderate-intensity resistance exercise training three times per week for 32 weeks. Semaglutide will be administered during the first 16 weeks, followed by a 16-week exercise-only period.

Participants assigned to this arm will receive standard of care treatment for Type 2 diabetes for 16 weeks and participate in supervised moderate-intensity resistance exercise training three times per week for 32 weeks. No semaglutide will be administered during the study period.

Participants assigned to this arm will receive injectable semaglutide once weekly for 16 weeks and participate in supervised balance-and-tone (BAT) exercise three times per week for 32 weeks. Semaglutide will be administered during the first 16 weeks, followed by a 16-week exercise-only period.

The registry classes the interventions as behavioral and drug.

More on the Plan

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.

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).

Who Took Part

164 planned participants were the target.

It was open to people of any sex aged from 65 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Male or female. Age ≥ 65 at the time of signing informed consent. Score \>24/30 on the Mini-Mental State Exam (MMSE). Score \>6/8 on the Lawton Instrumental Activities of Daily Living Scale (IADL).

The full record lists 13 inclusion and 2 exclusion criteria; among the exclusions: have a medical condition for which semaglutide or exercise is contraindicated.

How the Study Was Run

Design: randomized, factorial and single-blind.

The participants were allocated by chance, so the Semaglutide group and the comparison group should start out alike.

Only one side, usually the participants, was kept unaware of whether Semaglutide was given.

Those kept unaware of assignments: outcomes assessor.

It started in 2026-09-01 with completion listed for 2029-05-01.

It ran at 1 site in Canada.

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: Trail Making Test (TMT) Part A and B (time frame: Baseline (Week 0), Midpoint (Week 16), Endpoint (Week 32)).

It also tracked 35 secondary outcomes, for example Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11), Digit Span (Forward and Backward), Stroop Color-Word Test and Rey Auditory Verbal Learning Test (RAVLT).

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Semaglutide in 164 people.

Its status is not yet recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.