Oral Semaglutide for Type 2 Diabetes in Youth

(PIONEER TEENS Trial)

Not currently recruiting at 181 trial locations

Overseen By Novo Nordisk

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Metformin, Basal insulin

Disqualifiers: Type 1 diabetes, MODY, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

Duration: 66 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new medicine, oral semaglutide, for treating type 2 diabetes in children and teenagers. The study compares semaglutide to a placebo (a dummy pill) to determine its ability to manage blood sugar levels effectively and safely. Participants will take a tablet every morning before eating or drinking and will be monitored over a year through clinic visits and phone calls. Children and teenagers managing type 2 diabetes with treatments like metformin or insulin might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for type 2 diabetes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have a stable dose of metformin or basal insulin before joining. You may need to continue these medications during the trial.

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

Research has shown that oral semaglutide has been tested in several studies to assess its safety for people with type 2 diabetes. It effectively lowers blood sugar levels and aids in weight loss. Its safety profile is similar to that of a placebo, meaning it poses no greater risk than a harmless pill used in studies.

Previous trials in adults demonstrated that it does not increase heart risks compared to a placebo. This is significant because safety in children and teens often mirrors that observed in adults.

Some individuals might experience mild side effects, such as an upset stomach or nausea, which are common with many diabetes treatments. Overall, evidence suggests that oral semaglutide is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 2 diabetes?

Researchers are excited about oral semaglutide for treating type 2 diabetes in youth because it offers a convenient oral option compared to traditional injectable treatments like insulin. This medication is part of a class known as GLP-1 receptor agonists, which help improve blood sugar control by increasing insulin secretion, reducing appetite, and slowing digestion. Unlike many existing treatments that require injections, oral semaglutide allows for easier administration, potentially increasing adherence among young patients.

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

Research has shown that oral semaglutide, which participants in this trial may receive, effectively lowers blood sugar levels in people with type 2 diabetes. In earlier studies, it reduced glycated hemoglobin—a measure of blood sugar control—more than a placebo did, indicating better diabetes management than not taking the active medicine. Additionally, semaglutide has helped with weight loss, which can also benefit people with diabetes. These promising results suggest semaglutide might be a good option for managing type 2 diabetes in young people. ^{2 3 6 7 8}

Who Is on the Research Team?

Clinical Reporting Anchor and Disclosure (1452)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged 10 to under 18 with type 2 diabetes, who are on a stable dose of insulin or metformin. They must have an HbA1c level between 6.5%-11.0%. Participants cannot join if they have type 1 diabetes, certain diabetes-related antibodies, or other forms of diabetes like MODY.

Inclusion Criteria

I have been on a stable dose of metformin and basal insulin for at least 30 days.

I am between 10 and 17 years old.

Informed consent from parent(s) or legally acceptable representative (LAR) and child assent from the subject obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.

Exclusion Criteria

I have positive IA-2 or anti-GAD antibodies.

I have been diagnosed with MODY.

I have been diagnosed with type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo tablets daily for type 2 diabetes management

66 weeks

12 clinic visits, 8 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Semaglutide
• Placebo (Semaglutide)

Trial Overview The study tests oral semaglutide (a new medicine) against a placebo (dummy medicine). It aims to see how effective and safe semaglutide is in young people with type 2 diabetes over approximately one year, involving clinic visits and phone calls.

How Is the Trial Designed?

Group I: Semaglutide - max. tolerated dose Experimental Treatment 1 Intervention

Participants will receive semaglutide tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise.

Group II: Placebo (semaglutide) Placebo Group 1 Intervention

Participants will receive semaglutide placebo tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise.

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

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

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]

Oral semaglutide is the first FDA-approved oral GLP-1 receptor agonist for type 2 diabetes, showing effectiveness in reducing blood sugar levels and body weight in patients with uncontrolled diabetes, while maintaining a safety profile similar to injectable GLP-1RAs.

It is particularly beneficial for patients with inadequate glycemic control on other medications, those needing weight loss, and those at risk of hypoglycemia, but it is contraindicated in individuals with a history of certain thyroid cancers and pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how? Brunton, SA., Mosenzon, O., Wright, EE.[2020]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively improve blood sugar control and promote weight loss, with a favorable safety profile similar to other GLP-1RAs, based on extensive phase 3 trials including cardiovascular outcome studies.

The most common side effects of semaglutide are mild-to-moderate gastrointestinal disturbances, and while there are concerns about pancreatic and thyroid cancer, no unexpected safety issues have been identified, making it a beneficial option for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. Smits, MM., Van Raalte, DH.[2023]

Semaglutide significantly reduced HbA1c levels in both non-elderly (1.2%-1.5%) and elderly (1.3%-1.5%) patients with type 2 diabetes compared to comparators, demonstrating its efficacy across age groups.

The safety profile of semaglutide was comparable in both age groups, with no increased risk of severe hypoglycemia, making it a suitable treatment option for elderly patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Warren, M., Chaykin, L., Trachtenbarg, D., et al.[2022]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

Oral semaglutide, the first oral GLP-1 receptor agonist for type 2 diabetes, demonstrated the lowest cost of control for achieving key treatment targets compared to empagliflozin, sitagliptin, and liraglutide, based on data from the PIONEER clinical trials.

For endpoints like achieving HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide was significantly more cost-effective, with savings of up to $15,036 compared to other medications, indicating its potential for better economic value in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Cost Per Patient Achieving Treatment Targets with Oral Semaglutide: A Short-Term Cost-Effectiveness Analysis in the United States. Hunt, B., Hansen, BB., Ericsson, Å., et al.[2022]

In a meta-analysis of six randomized controlled trials involving 3962 overweight or obese individuals, subcutaneous semaglutide 2.4 mg administered weekly resulted in significant and sustainable weight loss, with an average reduction of 11.8% in body weight compared to placebo.

Semaglutide was well tolerated, with the most common side effects being mild to moderate gastrointestinal issues, indicating a favorable safety profile for non-diabetic overweight or obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial. Qin, W., Yang, J., Deng, C., et al.[2023]

Oral semaglutide significantly reduced HbA1c levels by 1.0 to 1.5% and body weight by 2.2 to 5.0 kg in patients with type 2 diabetes, regardless of their background medications, indicating its broad efficacy across different treatment regimens.

The safety profile of oral semaglutide was consistent across various background medication subgroups, with no significant increase in adverse events, making it a suitable option for patients using other glucose-lowering agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Pratley, RE., Crowley, MJ., Gislum, M., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2208601

Once-Weekly Semaglutide in Adolescents with Obesity A loss of body weight of at least 10% occurred in 62% of the participants in the semaglutide group and in 8% in the placebo group; a loss of at least 15% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10567925/

Unmet Needs in the Treatment of Childhood Type 2 Diabetes Results demonstrated that use of empagliflozin led to clinically relevant reductions in A1c, whereas linagliptin did not have this effect. Compared to placebo, ...

3. diatribe.org diatribe.org/diabetes-research/join-trial-testing-oral-semaglutide-preteens-and-teens-type-2-diabetes

Join a Trial Testing Oral Semaglutide in Preteens and ... This study will investigate how safe and effective an oral version of semaglutide is in preteens and teens with type 2 diabetes.

4. withpower.com withpower.com/trial/phase-3-diabetes-mellitus-10-2020-6460d

Oral Semaglutide for Type 2 Diabetes in Youth These trials found that oral semaglutide reduced glycated hemoglobin (a measure of blood sugar control) more effectively than placebo and some other diabetes ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-oral-semaglutide-compared-to-placebo-in-children-and-adolescents-with-type-2-diabetes-using-metformin-or-basal-insulin/

Study on the Effectiveness and Safety of Oral Semaglutide ... This study tests the effectiveness and safety of oral semaglutide for controlling blood sugar levels in children and adolescents with type 2 diabetes, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7364672/

Efficacy, Safety, and Tolerability of Oral Semaglutide ... Oral semaglutide was superior to placebo in reducing HbA 1c and body weight when added to insulin with or without metformin in patients with type 2 diabetes.

7. 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.

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.695182/full

Efficacy and Safety of Subcutaneous and Oral Semaglutide ... Our results also showed the superiority of oral semaglutide administration over other anti-diabetic drugs in reducing body weight (WMD: −1.53 kg ...