SGLT2 Inhibitors and Cognitive Function in Adults With Type 2 Diabetes (SaveMinD)

NCT07694596 | Active Not Recruiting DMC

• 1 other identifier: 0120-64/2026-2711-6
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, open-label trial with blinded outcome assessment (PROBE design) designed to evaluate the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy on cognitive function in adults with type 2 diabetes mellitus (T2D). A total of 200 participants aged 50 years or older with T2D of at least five years' duration and HbA1c ≤8.5% will be randomized in a 1:1 ratio to receive either standard diabetes care plus an SGLT2 inhibitor or standard diabetes care without an SGLT2 inhibitor. Participants will be followed for 12 months. The primary objective is to compare changes in executive cognitive function between the two treatment groups using a composite cognitive outcome derived from standardized neuropsychological tests. Secondary objectives include assessment of global cognitive function, glycaemic variability measured by continuous glucose monitoring, metabolic control, circulating biomarkers of neurodegeneration and inflammation, functional status, and treatment safety. Baseline brain magnetic resonance imaging (MRI), APOE genotyping, frailty status, sleep quality, psychological well-being, and physical activity will be evaluated as potential modifiers of cognitive outcomes and treatment response. The study is intended to provide prospective evidence regarding the association between SGLT2 inhibitor therapy and cognitive outcomes in adults with T2D while exploring the metabolic, neurodegenerative, and behavioural factors that may contribute to cognitive changes over time.

Conditions

Type 2 Diabetes Mellitus (T2DM); Cognitive Dysfunction

Keywords

Type 2 Diabetes Mellitus; SGLT2 inhibitors; cognitive decline; mild cognitive impairment; Executive Function; Glycemic Variability; Neurodegeneration; Diabetes-Related Cognitive Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change in Executive Cognitive Composite Score

  The primary outcome is the between-group difference in change from baseline to Month 12 in the Executive Cognitive Composite Score. The Executive Cognitive Composite Score is a standardized composite measure of executive function and processing speed calculated by averaging z-scores from the Digit Symbol Substitution Test, Trail Making Test Part A and Part B (using the Part B minus Part A completion time), the Digit Span Backward Test, and Verbal Fluency Tests (letter fluency and semantic/category fluency). The composite score is expressed as a standardized z-score and therefore has no fixed theoretical minimum or maximum value. Higher scores indicate better executive cognitive performance.

  Baseline to 12 months

Secondary Outcomes (17)

• Change in Montreal Cognitive Assessment (MoCA) Score

  Baseline to 12 months

• Change in Glycaemic Variability Assessed by Continuous Glucose Monitoring

  Baseline, 6 months, and 12 months

• Change in HbA1c

  Baseline, 6 months, and 12 months

• Change in High-Sensitivity C-Reactive Protein (hsCRP)

  Baseline to 12 months

• Change in Neurofilament Light Chain (NfL)

  Baseline to 12 months

Study Arms (2)

Standard Diabetes Care + SGLT2 Inhibitor

EXPERIMENTAL

Participants randomized to the intervention group will receive guideline-directed standard diabetes care plus treatment with an SGLT2 inhibitor (empagliflozin or dapagliflozin) according to routine clinical practice. Participants will be followed for 12 months.

Drug: SGLT2 Inhibitor; Other: Standard Diabetes Care

Standard Diabetes Care

ACTIVE COMPARATOR

Participants randomized to the comparator group will receive guideline-directed standard diabetes care without initiation of SGLT2 inhibitor therapy during the study period.

Other: Standard Diabetes Care

Interventions

SGLT2 Inhibitor DRUG

Participants randomized to the intervention group will receive empagliflozin (10 mg once daily, with optional titration to 25 mg according to clinical judgement and tolerability) or dapagliflozin (10 mg once daily) in addition to standard diabetes care. The choice of SGLT2 inhibitor will be made by the treating investigator according to routine clinical practice.

Also known as: empagliflozin or dapagliflozin

Standard Diabetes Care + SGLT2 Inhibitor

Standard Diabetes Care OTHER

Individualized diabetes management according to current national and international clinical practice guidelines, including lifestyle counselling and glucose-lowering therapy as clinically indicated. Both study groups will receive standard diabetes care throughout the study.

Also known as: Guideline-Directed Standard Diabetes Care

Standard Diabetes Care; Standard Diabetes Care + SGLT2 Inhibitor

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults aged 50 years or older.
• diagnosis of type 2 diabetes mellitus according to current American Diabetes - - association (ADA) diagnostic criteria.
• duration of type 2 diabetes mellitus of at least 5 years.
• glycated haemoglobin (HbA1c) ≤8.5% (≤69 mmol/mol) at screening.
• estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m².
• stable glucose-lowering therapy for at least 3 months before enrolment.
• able to complete neuropsychological assessments and all study procedures.
• willing and able to wear a continuous glucose monitoring (CGM) sensor and a physical activity monitor.
• able to provide written informed consent.

You may not qualify if:

• previous or current treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor.
• Montreal Cognitive Assessment (MoCA) score \<20 at screening.
• diagnosis of dementia or another major neurocognitive disorder.
• history of stroke or transient ischaemic attack within the previous 6 months.
• Parkinson's disease, multiple sclerosis, epilepsy, or another major neurological disorder affecting cognitive function.
• severe psychiatric illness likely to interfere with study participation or cognitive assessment.
• estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m².
• history of diabetic ketoacidosis.
• recurrent urinary tract infections (≥3 episodes during the previous year).
• contraindication to magnetic resonance imaging (MRI).
• pregnancy, breastfeeding, or planned pregnancy during the study period.
• active malignancy requiring systemic treatment (except adequately treated non-melanoma skin cancer).
• moderate or severe hepatic impairment (Child-Pugh Class B or C).
• alcohol or substance abuse likely to interfere with study participation.
• presence of an established indication for mandatory SGLT2 inhibitor therapy according to current international clinical practice guidelines (e.g., symptomatic heart failure or chronic kidney disease).

Sponsors & Collaborators

• University of Primorska: lead
• University of Ljubljana, Faculty of Medicine: collaborator

Study Sites (1)

Health Center

Koper, 6000, Slovenia

Location

Related Publications (1)

• Shin A, Koo BK, Lee JY, Kang EH. Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study. BMJ. 2024 Aug 28;386:e079475. doi: 10.1136/bmj-2024-079475.

  PMID: 39197881 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cognitive Dysfunction; Nerve Degeneration

Interventions

Sodium-Glucose Transporter 2 Inhibitors; empagliflozin; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study follows a Prospective Randomized Open-label Blinded Endpoint (PROBE) design. Owing to the nature of the intervention, participants and treating physicians will not be blinded to treatment allocation. However, investigators performing cognitive assessments, data management, and statistical analyses will remain blinded throughout the study. Laboratory personnel responsible for biomarker analyses will also be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Internal Medicine Specialist

Model Details: Participants will be randomized in a 1:1 ratio to receive either standard diabetes care plus an SGLT2 inhibitor or standard diabetes care without initiation of an SGLT2 inhibitor. Randomization will be centrally performed using a computer-generated allocation sequence and stratified by age and educational attainment to minimize potential confounding related to cognitive performance. Participants will be followed prospectively for 12 months.

Study Record Dates

• First Submitted: June 28, 2026
• First Posted: July 10, 2026
• Study Start: June 20, 2026
• Primary Completion (Estimated): April 20, 2028
• Study Completion (Estimated): April 20, 2028
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)