Semaglutide for Type 2 Diabetes

Overseen By Francis Kim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how semaglutide, a diabetes medication administered via auto-injector, affects brain blood flow in individuals with type 2 diabetes. Researchers will compare semaglutide to a placebo (a non-active treatment) to evaluate its impact on the brain’s blood vessels. They hope semaglutide might improve blood flow and offer protection against strokes. Suitable participants have had type 2 diabetes for at least three years and are managing it with medications like insulin or metformin. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for semaglutide?

Research has shown that semaglutide is generally safe for people with type 2 diabetes. In a large study, 5.1% of patients stopped using it due to side effects, while serious side effects affected only 0.5% of patients. Another study with over 3,000 patients found that semaglutide was safe when added to their regular diabetes treatment. Real-world data confirmed that semaglutide helped lower weight and blood sugar levels and was well-tolerated by most patients. The FDA has already approved this treatment for managing type 2 diabetes, indicating a strong safety record. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Type 2 Diabetes, which often include oral medications and insulin injections, semaglutide is unique because it is delivered via an auto-injector, offering a more convenient and potentially less painful option for patients. Semaglutide works by mimicking a hormone called GLP-1, which helps regulate blood sugar levels by enhancing insulin secretion and slowing down digestion. Researchers are excited about semaglutide because it not only effectively lowers blood sugar but also has the added benefit of promoting weight loss, which can be a significant advantage for managing Type 2 Diabetes.

What is the effectiveness track record for semaglutide in treating type 2 diabetes?

Research shows that semaglutide works well for people with Type 2 Diabetes (T2D). Studies have found that it helps lower body weight, body mass index (BMI), and HbA1c levels, a measure of long-term blood sugar. Additionally, semaglutide has been linked to a 20% decrease in major heart-related events, such as heart attacks or strokes. This medication is already approved and used for these benefits, proving its effectiveness in managing diabetes-related conditions. In this study, participants will receive either semaglutide or a placebo at random. Researchers expect semaglutide to improve blood flow in the brain, potentially benefiting people with T2D. ^{3 5 6 7 8}

Who Is on the Research Team?

Francis Kim, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

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 am between 40 and 65 years old.

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide Auto-Injector

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Ozempic for:

• Type 2 diabetes
• Reducing the risk of major adverse cardiovascular events

Approved in United States as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in United States as Rybelsus for:

• Type 2 diabetes

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Reducing the risk of major adverse cardiovascular events

Approved in European Union as Wegovy for:

• Chronic weight management in adults with obesity or overweight

Approved in European Union as Rybelsus for:

• Type 2 diabetes

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+

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9889982/

Real world effectiveness of subcutaneous semaglutide in ... The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world.

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.15911

Semaglutide use in people with obesity and type 2 diabetes ... This real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2032183

Once-Weekly Semaglutide in Adults with Overweight or ... Analyses from the DXA substudy suggested that semaglutide led to greater reduction in fat mass than lean body mass, a finding consistent with ...

4. nature.com nature.com/articles/s41591-024-02996-7

Long-term weight loss effects of semaglutide in obesity ... In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2840010

Liraglutide vs Semaglutide vs Dulaglutide in Veterans With ... This comparative effectiveness study examines risks of kidney, cardiovascular, and death outcomes among patients with type 2 diabetes ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39118222/

Real-world safety profile of once-weekly semaglutide in ... In total, 5.1% of patients reported AEs that led to treatment discontinuation, 0.5% reported serious adverse drug reactions and 0.2% had an AE ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1607141

Semaglutide and Cardiovascular Outcomes in Patients ... We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1871402124000857

Efficacy and safety of oral semaglutide in type 2 diabetes This retrospective cohort study showed −1.1 % HbA1c reduction, −3.5 kg weight loss, −1.1 kg/m2 BMI decrease (p < 0.001 for all), and 32.4 % of patients achieved ...