NCT07485062

Brief 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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
164

participants targeted

Target at P75+ for phase_4 type-2-diabetes

Timeline
37mo left

Started May 2026

Typical duration for phase_4 type-2-diabetes

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
May 2026May 2029

First Submitted

Initial submission to the registry

February 11, 2026

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 20, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

May 1, 2026

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2029

Last Updated

March 20, 2026

Status Verified

March 1, 2026

Enrollment Period

3 years

First QC Date

February 11, 2026

Last Update Submit

March 16, 2026

Conditions

Type 2 DiabetesCognitive Decline in Older Adults

Keywords

Exercise TrainingSemaglutideBrain HealthCognitive FunctionOlder AdultsPhysical ActivityType 2 Diabetes

Outcome Measures

Primary Outcomes (1)

  • Trail Making Test (TMT) Part A and B

    Executive function will be assessed using the Trail Making Test (TMT), Parts A and B. The TMT measures visual attention, processing speed (Part A), and executive function/set-shifting ability (Part B). Time to completion (seconds) will be recorded, with faster completion times indicating better performance.

    Baseline (Week 0), Midpoint (Week 16), Endpoint (Week 32)

Secondary Outcomes (35)

  • Montreal Cognitive Assessment (MoCA)

    Baseline (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • Mini-Mental State Examination (MMSE)

    Baseline (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11)

    Baseline (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • Digit Span (Forward and Backward)

    Baseline (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • Stroop Color-Word Test

    (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • +30 more secondary outcomes

Other Outcomes (8)

  • Total Lean Body Mass (LBM)

    Baseline (Week 0), Midpoint (Week 16), and Endpoint (Week 32)

  • Body Fat Percentage (%BF)

    Baseline (0 weeks), Midpoint (16 weeks), Endpoint (32 weeks)

  • Bone Mineral Density (BMD)

    Baseline (0 weeks), Midpoint (16 weeks), Endpoint (32 weeks)

  • +5 more other outcomes

Study Arms (4)

Resistance Exercise + Semaglutide

EXPERIMENTAL

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.

Drug: semaglutideBehavioral: Moderate-Intensity Resistance Exercise

Standard of Care + Resistance Exercise

ACTIVE COMPARATOR

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.

Behavioral: Moderate-Intensity Resistance Exercise

Semaglutide + Balance and Tone Exercise

ACTIVE COMPARATOR

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.

Drug: semaglutideBehavioral: Balance and Tone (BAT) Exercise

Standard of Care + Balance and Tone Exercise

ACTIVE COMPARATOR

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

Behavioral: Balance and Tone (BAT) Exercise

Interventions

Moderate-Intensity Resistance ExerciseBEHAVIORAL

Supervised moderate-intensity resistance exercise training performed three times per week for 32 weeks.

Resistance Exercise + SemaglutideStandard of Care + Resistance Exercise
Balance and Tone (BAT) ExerciseBEHAVIORAL

Supervised balance-and-tone (BAT) exercise performed three times per week for 32 weeks, serving as an active control exercise condition.

Semaglutide + Balance and Tone ExerciseStandard of Care + Balance and Tone Exercise
semaglutideDRUG

Injectable semaglutide administered once weekly by subcutaneous injection for 16 weeks, as prescribed and monitored by the study physician.

Resistance Exercise + SemaglutideSemaglutide + Balance and Tone Exercise

Eligibility Criteria

Age65 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • 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.
  • Community-dwelling
  • Male or female
  • Age ≥ 65 at the time of signing informed consent
  • Glycated hemoglobin levels of ≥7% (i.e., A1c levels high enough to see intervention-related changes and increase eligibility for recruitment, but can exercise safely)
  • Eligible for the Ontario Drug Benefit (inadequate glycemic control and on max tolerated dose of metformin or metformin contraindicated or inappropriate)
  • Score \>24/30 on the Mini-Mental State Exam (MMSE)
  • Score \>6/8 on the Lawton Instrumental Activities of Daily Living Scale (IADL)
  • Have visual acuity of \>20/40 with or without corrective lenses
  • Speak and understand English fluently
  • Complete the Physical Activity Readiness Questionnaire (PAR-Q+) and obtain physician clearance to start a supervised exercise program
  • Comfortable with a blood draw
  • Not currently engaging in structured resistance exercise more than once per week

You may not qualify if:

  • Have a medical condition for which semaglutide or exercise is contraindicated
  • Use of a GLP-1 receptor agonist in the past 6 months (i.e., offers removal of Semaglutide from the system as it has a half-life of around 1 week; thus, 8-10 weeks are required for a washout.
  • \) Have engaged regularly (\>1/week) in aerobic or RE within the past 6 months 4) Have a neurodegenerative disease (i.e., dementia) or psychiatric condition 5) Have had untreated depression in the past 6 months (6) Have experienced a recent vascular incident (i.e., stroke, myocardial infarction in the last 6 months.) (7) Have severe peripheral neuropathy, an active foot wound, or severe musculoskeletal/joint disease (8) Active or untreated retinopathy (9) Taking psychotropic medications (excluding those for the treatment of depression)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Western University

London, Ontario, N6A 3K7, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Motor Activity

Interventions

semaglutideglycine N-choloyltransferaseExercise

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesBehavior

Intervention Hierarchy (Ancestors)

Motor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Olivia Ghosh-Swaby, PhD

CONTACT

5196612111oghoshsw@uwo.ca

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 11, 2026

First Posted

March 20, 2026

Study Start

May 1, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Last Updated

March 20, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Individual participant data will not be shared with external researchers. The study protocol and informed consent documents do not include provisions for individual participant data sharing, and data are managed and stored in accordance with institutional research ethics board requirements.

Locations

CA(1)