Anti-Diabetic Medications for Parkinson's Disease and Lewy Body Dementia

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must be taking: DPP4 inhibitors, SGLT2 inhibitors

Must not be taking: Insulin, Anticoagulants, Chemotherapy, others

Disqualifiers: Renal impairment, Bleeding disorder, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the diabetes medications dapagliflozin and sitagliptin can alleviate neurological symptoms in individuals with Parkinson's disease or Lewy body dementia. The researchers aim to determine if these medications are well tolerated and offer brain-related benefits. Participants will be divided into groups receiving either dapagliflozin, sitagliptin, or a placebo (a harmless pill with no active drug). Ideal candidates for this trial include those diagnosed with Parkinson's or Lewy body dementia who also have mild diabetes or glucose issues and have maintained stable treatment for the past three months. As a Phase 4 trial, this research focuses on understanding how these FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you do not use insulin or other anti-diabetes medications except for metformin. If you are taking any other anti-diabetes drugs, you would need to stop them to participate.

What is the safety track record for dapagliflozin and sitagliptin?

Research has shown that dapagliflozin, a type of medication, is usually well-tolerated. Studies have found that people taking this medication have a 20% lower chance of developing dementia compared to those using other drugs. This suggests potential benefits for brain health, making it a promising option for conditions like Parkinson's disease.

Early research indicates that sitagliptin, another medication, is safe and does not increase the risk of Parkinson's disease. Some studies even suggest it might benefit brain health in people with type 2 diabetes.

Both dapagliflozin and sitagliptin are commonly used to manage diabetes, and their safety is well-established from these uses. While researchers are now testing them for new brain health benefits, existing research supports their general safety in humans. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using dapagliflozin and sitagliptin for Parkinson's Disease and Lewy Body Dementia because these drugs bring a fresh approach to treatment. Unlike the usual treatments that focus primarily on managing symptoms of these neurological conditions, dapagliflozin and sitagliptin are anti-diabetic medications that target glucose metabolism. This novel mechanism of action could potentially offer neuroprotective benefits, reducing the progression of these diseases. Dapagliflozin works by helping the body eliminate excess glucose through urine, while sitagliptin increases insulin production and decreases the liver's glucose output. These unique actions might provide new hope for slowing down or altering the course of these challenging conditions.

What evidence suggests that this trial's treatments could be effective for Parkinson's disease and Lewy body dementia?

In this trial, participants will join different treatment arms to evaluate the effects of anti-diabetic medications on Parkinson's Disease and Lewy Body Dementia. Research has shown that SGLT2 inhibitors, like dapagliflozin, which the Dapagliflozin Group will receive, may reduce the risk of dementia by about 20-22%. However, no clear evidence links dapagliflozin to Parkinson's disease (PD). Meanwhile, participants in the Sitagliptin Group will receive sitagliptin, a DPP-4 inhibitor. Animal studies of PD have found that sitagliptin improves memory by increasing BDNF levels, which help maintain brain health. While these results are encouraging, evidence of sitagliptin's effects on Parkinson's in humans remains limited. Overall, both treatments show potential benefits for brain health, but more research on humans is needed. ^{4 5 6 7 8}

Who Is on the Research Team?

Jessica Wilson, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's disease or Lewy body dementia. Specific criteria for joining are not provided, but typically participants must meet certain health standards and may be required to have a specific stage of the diseases.

Inclusion Criteria

I have Parkinson's or Lewy Body Dementia and my treatment hasn't changed in the last 3 months.

I have pre-diabetes or mild diabetes according to the American Diabetes Association.

Exclusion Criteria

I have a bleeding disorder or I'm on blood thinners.

I am currently taking high doses of steroids.

I cannot take certain diabetes medications due to allergies, past swelling reactions, pancreatitis, gallbladder issues, or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either dapagliflozin, sitagliptin, or placebo for the treatment period

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Sitagliptin

Trial Overview The study is testing two types of diabetes medications, Sitagliptin (a DPP4 inhibitor) and Dapagliflozin (an SGLT2 inhibitor), against a placebo to see if they can help with neurological symptoms in Parkinson's disease and Lewy body dementia.

How Is the Trial Designed?

Group I: Sitagliptin Group Experimental Treatment 1 Intervention

Subjects will receive sitagliptin for the approximately 4-week treatment period.

Group II: Dapagliflozin Group Experimental Treatment 1 Intervention

Subjects will receive dapagliflozin for the approximately 4-week treatment period.

Group III: Placebo Group Placebo Group 1 Intervention

Subjects will receive placebo for the approximately 4-week treatment period.

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40146049/

Association between dapagliflozin and risk of dementia ... Conclusions: This sub-analysis found no significant association between dapagliflozin and reduced risks of dementia or PD. While these results ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000209805

SGLT2 Inhibitor Use and Risk of Dementia and Parkinson ... For the secondary composite outcomes, SGLT2i use was associated with a 21% decrease in the risk of all-cause dementia and a 22% decrease in the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11350016/

Heterogeneous treatment effects of sodium‐glucose ... Interpretation: Our study found a decreased risk of all‐cause dementia associated with SGLT2 inhibitors. In addition, the association may be ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0168822725004449

Association between SGLT2 inhibitor therapy and ... Patients taking SGLT2 inhibitors had a 20 % lower risk of developing dementia than those receiving DPP-4 inhibitors, with the effect being most pronounced in ...

5. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2831975

Cardioprotective Glucose-Lowering Agents and Dementia ... Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11676485/

New Insights into the Role of SGLT-2 Inhibitors in the ... SGLT-2 inhibitors, such as empagliflozin and dapagliflozin, may have neuroprotective effects that reduce dementia risk and improve cognitive function in type 2 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12404899/

Real‐world observations of GLP‐1 receptor agonists and ... Sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors are significantly associated with a reduced risk of AD compared to dipeptidyl peptidase‐4 ( ...

8. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04018-w

The pharmacodynamics-based prophylactic benefits of GLP-1 ... Among all investigated medications, only dapagliflozin demonstrated significant prophylactic benefits, specifically in preventing Parkinson's ...