Semaglutide for Type 2 Diabetes

Overseen by Francis Kim, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Washington

Must be taking: Insulin, Metformin

Must not be taking: GLP-1 antagonists, Pioglitazone

Disqualifiers: Kidney dysfunction, Hypertension, Stroke, others

Prior Safety Data

Approved in 12 Jurisdictions

Trial Summary

What is the purpose of this trial?

A human subjects research study, the primary purpose of which is to assess the EFFECTS OF SEMAGLUTIDE ON INTRACRANIAL BLOOD FLOW AND BLOOD-BRAIN BARRIER PERMEABILITY IN TYPE-2 DIABETES (T2D) through testing of the intervention on patients in a clinical setting. The study will randomize subjects with diabetes to either semaglutide or matching placebo. Magnetic resonance images will be primary endpoint measured at baseline and at one year to assess effect of this FDA approved medication. Given the available evidence supporting the neuroprotective effect of this drug class and stroke reduction with semaglutide, and the investigators preliminary data showing that T2D had significantly reduced total number of distal arterial branches in the brain than non-T2D, the investigators expect treatment with semaglutide will be associated with improved intracranial blood flow condition.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you cannot participate if you are currently treated with a glucagon-like peptide-1 receptor antagonist or have used pioglitazone in the past 3 months.

What data supports the effectiveness of the drug semaglutide for type 2 diabetes?

Research shows that semaglutide, available as Ozempic and Rybelsus, effectively lowers blood sugar and helps with weight loss in people with type 2 diabetes. Clinical trials have demonstrated its benefits over other similar treatments, and it is approved for use in several countries. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been tested in many clinical trials for type 2 diabetes and has shown a safety profile similar to other drugs in its class. It is generally well-tolerated, with cardiovascular safety comparable to a placebo in high-risk patients. ^{1 2 3 4 6}

How is the drug semaglutide unique for treating type 2 diabetes?

Semaglutide is unique because it is available both as a once-weekly injection (Ozempic) and as the first oral GLP-1 receptor agonist (Rybelsus), offering flexibility in administration. It effectively lowers blood sugar and promotes weight loss, and the oral form uses an absorption enhancer to facilitate its uptake in the body. ^{1 2 3 4 7}

Research Team

Francis Kim, MD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for men and women aged 40-65 with type-2 diabetes for at least 3 years, HbA1C levels between 7%-10%, and on stable blood sugar control medications. Excluded are those needing high insulin doses, pregnant or breastfeeding women, individuals with uncontrolled hypertension, a history of pancreatitis or certain cardiovascular events, family history of specific carcinomas or syndromes, severe kidney issues, recent pioglitazone treatment, or contraindications to MRI.

Inclusion Criteria

Willing to participate and sign informed consent.

I have had type-2 diabetes for 3+ years and my HbA1C is between 7%-10% while on medication.

I am between 40 and 65 years old.

Exclusion Criteria

I have taken pioglitazone in the last 3 months.

I have had pancreatitis before.

I am not pregnant, breastfeeding, or planning to become pregnant in the next 15 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either semaglutide or placebo for 1 year

52 weeks

Regular visits for monitoring and glucose management

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Semaglutide Auto-Injector (Glucagon-like peptide-1 receptor agonist)

Trial Overview The study tests the effects of Semaglutide versus placebo on intracranial blood flow and brain-barrier permeability in people with type-2 diabetes. Participants will be randomly assigned to receive either Semaglutide via auto-injector or a placebo. The main outcome will be measured using magnetic resonance images taken at baseline and after one year.

Participant Groups

Group I: Active Active Control 1 Intervention

Subjects randomized to semaglutide for 1 year.

Group II: Placebo Placebo Group 1 Intervention

Subjects randomized to placebo for 1 year.

Semaglutide Auto-Injector is already approved in Canada, Canada, Japan, Japan for the following indications:

Approved in Canada as Ozempic for:

• Type 2 diabetes

Approved in Canada as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in Japan as Ozempic for:

• Type 2 diabetes

Approved in Japan as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

In a meta-analysis of 23 randomized trials involving 22,096 patients with type 2 diabetes, semaglutide was not found to significantly increase the overall risk of diabetic retinopathy (DR) compared to control groups.

However, the analysis indicated that semaglutide was associated with a higher risk of DR in specific subgroups, particularly in patients aged 60 years or older and those with a diabetes duration of 10 years or more, suggesting that caution is warranted in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Wang, F., Mao, Y., Wang, H., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. [2019]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. [2022]

4. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. [2022]