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

Trial Summary

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.

What data supports the effectiveness of the drug semaglutide for obesity in patients with type 1 diabetes?

Semaglutide has been shown to provide significant and sustained weight loss in people with obesity, as demonstrated in the STEP clinical program. It is also used to treat type 2 diabetes, offering weight loss and cardiovascular benefits, which may suggest potential benefits for obesity in type 1 diabetes patients. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under names like Rybelsus and Ozempic, has been tested in many people with type 2 diabetes and is generally considered safe. It has a similar safety profile to other drugs in its class and does not increase heart-related risks compared to a placebo. ^{6 7 8 9 10}

How is the drug semaglutide unique for treating obesity in people with type 1 diabetes?

Semaglutide is unique because it is a once-weekly injection that not only helps with weight loss but also offers cardiovascular benefits, which is important for people with obesity and diabetes. Unlike other treatments, it has shown significant and sustained weight loss, making it a 'game changer' in obesity management. ^{1 3 4 9 11}

What is the purpose of this trial?

More than 40% of young adults with type 1 diabetes (T1D) also have overweight or obesity. Each of these diagnoses increase the risk of adverse cardiovascular events. GLP-1 analogues are anti-obesity medications that are cardioprotective in adults with type 2 diabetes, however evaluation of these agents in people with T1D has been limited to glycemic outcomes. Investigators aim to study the impact of GLP-1 analogue obesity treatment on markers of cardiometabolic risk in young adults with T1D and obesity.

Research Team

Michelle Van Name, MD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

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]

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, 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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. [2023]

4. Israel pubmed.ncbi.nlm.nih.gov

Subcutaneous Semaglutide Use for Weight Management: Practice and Attitudes of Physicians in Israel. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Future perspectives in diabesity treatment: Semaglutide, a glucagon-like peptide 1 receptor agonist (Review). [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

7. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. [2022]

9. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. [2019]