Semaglutide for Obesity with Type 1 Diabetes

Overseen By Rehema Mtawali

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: GLP-1 agonists, Adjunctive diabetes, Anti-obesity, others

Disqualifiers: Psychiatric conditions, Pancreatitis, Thyroid cancer, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: 52 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests semaglutide, a medication for weight management, in young adults with type 1 diabetes (T1D) who also have obesity. The researchers aim to determine if semaglutide can reduce heart-related risks associated with both T1D and obesity. Participants will receive either semaglutide or a placebo for comparison. This trial may suit young adults diagnosed with T1D for over a year, who also struggle with obesity and have stable insulin and glucose levels. As a Phase 2 trial, this research measures semaglutide's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop using any adjunctive diabetes therapies or anti-obesity medications, including any GLP-1 agonist, if you have used them within the past 6 months. You also cannot use lipid-lowering medications other than statins and omega-3 products.

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

Research shows that semaglutide is generally safe for most people. Some studies have examined its safety in various groups. For example, one study found that semaglutide helped people with obesity lose weight, even without type 2 diabetes, and reported no major safety issues. Another study demonstrated that semaglutide could reduce the risk of heart problems in people with diabetes.

However, less is known about the safety and effectiveness of semaglutide for people with type 1 diabetes and obesity. This means less information is available for this specific group compared to others. Since semaglutide is already used for other conditions, it suggests general safety for most people.

Overall, the trial aims to learn more about the effectiveness and safety of semaglutide for young adults with type 1 diabetes and obesity. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity with type 1 diabetes?

Most treatments for obesity in individuals with type 1 diabetes focus on lifestyle changes and insulin management. However, semaglutide is unique because it targets the glucagon-like peptide-1 (GLP-1) receptor, which helps regulate appetite and food intake. Unlike traditional methods that primarily focus on insulin control, semaglutide has the potential to significantly reduce weight by altering hunger signals in the brain. Researchers are excited about semaglutide because it offers a new approach by directly addressing the mechanisms of weight gain, which could lead to better management of obesity in people with type 1 diabetes.

What evidence suggests that semaglutide might be an effective treatment for obesity in young adults with type 1 diabetes?

Studies have shown that semaglutide helps people with obesity lose weight. In one study, participants taking semaglutide lost about 15% of their body weight on average. Another study found that it reduced the risk of heart problems, such as heart attacks, by about 20%. These results are important because they demonstrate that semaglutide not only aids in weight loss but may also protect the heart. In this trial, participants will receive either semaglutide or a placebo. While most research has focused on individuals without type 1 diabetes, these findings suggest semaglutide could also benefit those with type 1 diabetes and obesity. ^{1 3 5 6 7}

Who Is on the Research Team?

Michelle Van Name, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for young adults with type 1 diabetes who are also overweight or obese. It's designed to see if a medication that usually helps people with type 2 diabetes can reduce heart disease risk in this group.

Inclusion Criteria

I use a continuous glucose monitor and plan to keep using it.

I have been diagnosed with Type 1 Diabetes.

Stable reported BMI in the past 90 days (within 5%)

Exclusion Criteria

I use less than 0.5 units of insulin per kg of my body weight daily.

Contraindications to study medications, including: Personal history of pancreatitis, renal impairment, or known liver disease other than non-alcoholic hepatic steatosis, Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Type 2, Known or suspected allergy to semaglutide, excipients, or related products, Use of lipid lowering medications other than statins and omega-3 products, Previous randomization in this trial. Participants who enrolled but did not randomize can be re-screened. Potential reasons for enrolment without randomization include scheduling conflicts for the baseline studies, or for females, not yet meeting the highly effective methods of contraception criteria, Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures, Diabetic ketoacidosis in the past 6 months, Not meeting MRI safety criteria or claustrophobia preventing participation in the MRI, Anemia or known hematologic condition impacting HbA1c reading, or another medical condition that precludes participation, Treatment with another investigational drug or other intervention within the past 1 month, Subjects with a PHQ-9 score >15 or those found to have a lifetime history of suicide attempts, or suicidal ideation within the past 3 months on the C-SSRS, Corn allergy, Subjects with severe hypoglycemia requiring hospitalization in the past 3 months, Clinically significant gastroparesis

I have not used diabetes or weight loss medications in the last 6 months.

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 complete baseline assessments including Abdominal MRI, Euglycemic hyperinsulinemic clamp, DEXA scan, and High-fat mixed meal tolerance test

1-2 weeks

4 visits (in-person)

Treatment

Participants receive weekly semaglutide or placebo injections for 52 weeks

52 weeks

Weekly visits (in-person)

Wean Off

Participants undergo a 4-week wean off period from the study drug

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including insulin titration for 2 weeks

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The study tests the effects of Semaglutide, a GLP-1 analogue anti-obesity treatment, against a placebo. Participants will not know which one they're getting as it's randomly decided and both look the same.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

Participants in this arm will receive semaglutide (escalated to 2.4mg or max tolerated dose) weekly for 12 months. Then a 4 week wean period plus 2 weeks as needed insulin titration.

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive a matched placebo weekly for 12 months. Then a 4 week wean period plus 2 weeks as needed insulin titration.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

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, 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]

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]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

GLP-1 receptor agonists, like semaglutide, are effective in treating obesity and type 2 diabetes by promoting insulin secretion, inhibiting glucagon, and slowing gastric emptying, which can also lead to weight loss.

Semaglutide is notable for being the first long-acting GLP-1 RA available as an oral pill, and it has shown cardiovascular benefits along with potential side effects, making it a significant option for managing both diabetic and non-diabetic obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future perspectives in diabesity treatment: Semaglutide, a glucagon-like peptide 1 receptor agonist (Review). Tilinca, MC., Tiuca, RA., Niculas, C., et al.[2021]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[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]

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]

A survey of 127 physicians revealed that many have varying pre-treatment requirements for prescribing semaglutide for weight loss, with 30% requiring a minimum body mass index of 30 kg/m² and 67% expecting documented lifestyle changes.

Despite its effectiveness, over 50% of patients discontinued semaglutide therapy within the first 3 months, primarily due to cost, perceived lack of effectiveness, and concerns about long-term side effects, indicating a need for better patient education and support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Semaglutide Use for Weight Management: Practice and Attitudes of Physicians in Israel. Dicker, D., Tamir, O., Lieberman-Segal, G., et al.[2023]

Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective for treating type 2 diabetes and obesity, providing significant weight loss and cardiovascular benefits, making it crucial for high-risk patients.

However, during the SUSTAIN clinical trial program, a safety concern arose regarding the worsening of diabetic retinopathy, potentially linked to rapid reductions in HbA1c levels, which requires further investigation and careful clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. Cigrovski Berkovic, M., Strollo, F.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9758543/

Efficacy and Safety of Semaglutide for Weight Loss in ... Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared to ...

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

Once-Weekly Semaglutide in Adults with Overweight or ... 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.

3. 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 ...

4. vox.com vox.com/future-perfect/467025/ozempic-glp-1-drugs-obesity-weight-loss

The Ozempic effect is finally showing up in obesity data - Vox In large randomized trials, semaglutide 2.4 mg — the active ingredient used in medicines like Ozempic — produced about 15 percent average weight ...

5. 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 ... Body weight reductions of ≥5%, ≥10%, ≥15%, and ≥20% from baseline at 2 years were observed in 90.5%, 69.8%, 46.9%, and 29.6% of patients, ...

6. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40550013/

Semaglutide in Adults with Type 1 Diabetes and Obesity The efficacy and safety of semaglutide in adults with type 1 diabetes are not established. Methods: In this 26-week, double-blind trial, we randomly assigned 72 ...