Semaglutide for Type 2 Diabetes

(PORT Trial)

Overseen By Simeon I Taylor, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must be taking: GLP1R agonists

Disqualifiers: Diabetes, Allergy to semaglutide, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how semaglutide, a medication, affects insulin and glucose levels in people with Type 2 Diabetes. Researchers aim to understand how genetic differences in the Amish community influence the drug's ability to improve insulin response and glucose clearance. Participants will receive semaglutide injections for six weeks to observe its effects. The study seeks individuals of Amish descent with a BMI of 27 or higher who have not been diagnosed with diabetes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stop taking any drug, vitamin, or nutritional supplement that might alter the response to semaglutide, as judged by the research physician or principal investigators.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that semaglutide is generally safe, but a few considerations are important. In one study, only 5.1% of participants stopped using it due to side effects. Serious side effects were very rare, occurring in just 0.5% of participants. Some experienced stomach issues, so monitoring for this is advisable. Another study found a slight increase in heart rate over time for some individuals.

Semaglutide is also used for other conditions, such as diabetes, which supports its safety profile. However, since this is an early-phase study, researchers are still gathering safety information. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Type 2 Diabetes, which often include oral medications and insulin injections, semaglutide offers a novel approach by mimicking a hormone called GLP-1 that helps regulate blood sugar levels. Researchers are excited about semaglutide because it is administered as a once-weekly injection, which could improve convenience and adherence compared to daily medications. Additionally, semaglutide has shown potential not only in controlling blood sugar but also in promoting weight loss, which is a significant benefit for many patients with Type 2 Diabetes.

What evidence suggests that semaglutide might be an effective treatment for type 2 diabetes?

Research shows that semaglutide, the medication under study in this trial, effectively helps people with type 2 diabetes manage their condition and lose weight. Studies have found that it lowers blood sugar levels and body weight, with most people tolerating it well. Additionally, semaglutide has been linked to a reduced risk of heart-related issues, which is crucial for those with diabetes. These findings suggest it could benefit those managing type 2 diabetes, especially individuals who are overweight or obese. ^{2 6 7 8 9}

Who Is on the Research Team?

Amber L Beitelshees, PharmD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for overweight or obese individuals of Amish descent with a BMI of 27 kg/m2 or higher. It's not open to women who can have children and are sexually active, people with certain blood, liver, thyroid conditions, kidney issues (eGFR < 60 mL/min/1.73 sq. m.), a personal or family history of specific cancers, known allergy to semaglutide, or those on medications that could affect the study.

Inclusion Criteria

You weigh more than what is considered healthy for your height.

You are of Amish descent.

Exclusion Criteria

You are allergic to semaglutide.

Your hematocrit level is below 35%.

I cannot stop taking a medication or supplement that may affect the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline FSIVGTT and receive the first dose of semaglutide

1 day

1 visit (in-person)

Treatment

Participants self-administer semaglutide weekly for 6 weeks with home visits as needed

6 weeks

Home visits as needed

Post-Treatment Assessment

Participants undergo a second FSIVGTT within 1 week of the final dose of semaglutide

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The trial tests how Semaglutide affects insulin secretion and glucose disappearance in the body by comparing before and after use in participants. It involves genetic testing to find any variants linked to these effects using frequent blood sugar tests over six weeks.

How Is the Trial Designed?

Group I: Open label administration of semaglutide Experimental Treatment 1 Intervention

Semaglutide: 0.25 mg, sc, q.week for 4 weeks followed by 0.5 mg, sc, q.week for 2 weeks

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

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

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 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 (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&#174; tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

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]

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]

Citations

1. diabetesjournals.org diabetesjournals.org/diabetes/article/74/Supplement_1/1733-P/159240/1733-P-Two-Year-Real-World-Effectiveness-of

Two-Year Real-World Effectiveness of Semaglutide in Patients ... 85-OR: Semaglutide 2.4 mg Improves Patient Reported Outcome Measures of Physical Functioning in Adults with Overweight/Obesity and Type 2 ...

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/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes in Obesity ... Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes.

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. 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.

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. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4145254

Abstract 4145254: Effects Of Semaglutide On Safety ... Conclusion: In high cardiovascular risk T2DM patients, semaglutide was associated with a higher incidence of gastrointestinal disorders as ...

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 ...

9. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15794

Real‐world safety profile of once‐weekly semaglutide in ... Additionally, a CV outcomes trial reported an increased heart rate of more than 10 bpm in 16% of patients after 2 years of OW semaglutide ...