Semaglutide Tablets for Type 2 Diabetes

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Must not be taking: Prescription drugs

Disqualifiers: Hypersensitivity, Safety concerns, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how the body absorbs different versions of a new diabetes treatment called semaglutide, which manages blood sugar levels. Researchers will compare four types of semaglutide tablets to determine which one is most effective. Participants will take both an injection and oral tablets in different sequences, with assignments made randomly. The trial seeks healthy men with a body mass index (BMI) between 22.0 and 31.9. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription or non-prescription drugs, except for routine vitamins, topical medications, and occasional use of paracetamol (acetaminophen) and ibuprofen, at least 14 days before the study starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that semaglutide, the treatment being tested in this trial, is generally considered safe, though it can have side effects. When taken as a pill, common side effects include nausea, stomach pain, and diarrhea, which are the most frequently reported issues. Some individuals also experience vomiting and constipation, though these are less common.

For the injectable form of semaglutide, similar side effects have been observed, such as nausea and diarrhea. Some patients have also experienced reduced appetite and vomiting. These side effects are typical for many using semaglutide for type 2 diabetes.

This trial is in its early stages, focusing on how the body absorbs the medication rather than gathering extensive safety data. However, semaglutide is already approved for treating type 2 diabetes, suggesting it is generally considered safe for many when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about semaglutide tablets for type 2 diabetes because they offer a new oral option for a treatment that's typically given by injection. While most diabetes treatments like insulin and GLP-1 receptor agonists require injections, semaglutide tablets are taken orally, making it more convenient for patients. This new delivery method could improve patient compliance and comfort, potentially leading to better blood sugar control. Additionally, semaglutide works by mimicking a hormone that helps regulate blood sugar, offering a promising alternative to existing treatments.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes?

Research shows that semaglutide, available as a tablet or injection, effectively manages type 2 diabetes. In this trial, participants will receive different sequences of semaglutide treatments. Oral semaglutide has significantly lowered blood sugar levels (measured by HbA1c) and aided weight loss. One study found an average drop of 1.1% in HbA1c and a weight loss of 3.5 kg. The injectable form of semaglutide also delivers strong results, improving blood sugar control and aiding weight loss. Both forms enhance overall metabolic health and reduce heart-related risks. These findings support semaglutide as an effective treatment for type 2 diabetes. ^{5 6 7 8 9}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for healthy men who may be at risk of developing Type 2 Diabetes. Participants will be randomly assigned to receive one of four different tablet formulations of a medicine called semaglutide.

Inclusion Criteria

I am male.

Body mass index (BMI) between 22.0 and 31.9 kilogram per square meter (kg/m^2) at screening

Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram (ECG) and clinical laboratory tests performed during the screening visit, as judged by the investigator

Exclusion Criteria

Any condition which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol

Known or suspected hypersensitivity to study interventions or related products

I haven't taken any prescription drugs or non-prescription drugs, except for vitamins, topical medications, or occasional paracetamol/ibuprofen, in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive subcutaneously semaglutide B followed by oral semaglutide in different sequences

14 weeks

Treatment Period 2

Participants continue with oral semaglutide in different sequences

14 weeks

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 study aims to compare how the body absorbs the same dose of semaglutide when it's delivered in four distinct tablet forms, labeled as Semaglutide B, J, L, M, and N. The trial involves taking these tablets over a period of about 28 weeks.

How Is the Trial Designed?

Group I: Sequence 6: Semaglutide N then Semaglutide J Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide N then semaglutide J in treatment period 2.

Group II: Sequence 5: Semaglutide J then Semaglutide N Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide J then semaglutide N in treatment period 2.

Group III: Sequence 4: Semaglutide M then Semaglutide J Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide M then semaglutide J in treatment period 2.

Group IV: Sequence 3: Semaglutide J then Semaglutide M Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide J then semaglutide M in treatment period 2.

Group V: Sequence 2: Semaglutide L then Semaglutide J Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide L then semaglutide J in treatment period 2.

Group VI: Sequence 1: Semaglutide J then Semaglutide L Experimental Treatment 3 Interventions

Participants will receive subcutaneously semagutide B in treatment period 1 followed by oral semaglutide J then semaglutide L in treatment period 2.

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?

Novo Nordisk A/S

Lead 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 (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]

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]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[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 at doses of 7 mg and 14 mg significantly reduced hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes, with reductions of 1.06% and 1.10% respectively compared to placebo, based on a meta-analysis of 11 randomized controlled trials involving 9821 patients.

Both doses of semaglutide also led to significant weight loss, but the 14 mg dose was associated with a higher incidence of gastrointestinal side effects, such as nausea and vomiting, leading to more medication discontinuations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. Li, A., Su, X., Hu, S., et al.[2023]

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, 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]

Oral semaglutide, a new GLP-1 receptor agonist, significantly reduced glycated hemoglobin (HbA1c) levels by up to 1.4% after 26 weeks compared to placebo, indicating its efficacy in managing blood sugar levels in type 2 diabetes patients.

The treatment also led to greater body weight reductions compared to placebo and sitagliptin, with mild-to-moderate gastrointestinal side effects that typically decreased over time, suggesting it is a safe option with a low risk of severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. Lavernia, F., Blonde, L.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10391231/

The Effectiveness and Value of Oral Semaglutide for Type ... Results showed that oral semaglutide reduced HbA1c more than placebo, sitagliptin, and empagliflozin and more than liraglutide at 52 weeks but not at 26 weeks.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1901118

Oral Semaglutide and Cardiovascular Outcomes in ... In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo.

3. 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 ...

4. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15431

Real-world effectiveness and safety of oral semaglutide in ... Oral semaglutide was effective and safe for an unselected population, with one-third reporting weight loss >10% and about two-thirds achieving ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2657376

Effect of Oral Semaglutide Compared With Placebo and ... Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks.

6. novomedlink.com novomedlink.com/diabetes/products/treatments/rybelsus/efficacy-safety/safety-data.html

Safety data from RYBELSUS ® (semaglutide) clinical trials The most frequently reported adverse reactions were GI disorders, including nausea, abdominal pain, and diarrhea; Nausea, vomiting, and/or diarrhea occurred ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603723/

Semaglutide - StatPearls - NCBI Bookshelf Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/213051s018lbl.pdf

RYBELSUS tablets - accessdata.fda.gov In patients with type 2 diabetes, the mean population-PK estimated steady-state concentrations following once daily oral administration of 7 and 14 mg ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/semaglutide-oral-route/description/drg-20492085

Semaglutide (oral route) - Side effects & dosage This medicine is also used to lower the risk of heart attack, stroke, or death in patients with type 2 diabetes who are at high risk for these events.