Semaglutide + Automated Insulin System for Type 1 Diabetes

(SEMA SMA Trial)

Overseen By Nicholas Sabelli, B.Sc. (Hons)

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must be taking: Insulin

Must not be taking: GLP1-RAs, Anti-hyperglycemics

Disqualifiers: Pregnancy, Pancreatitis, Thyroid cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

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: Unknown

Duration: 24 weeks

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage type 1 diabetes by combining an automated insulin system, often called an "artificial pancreas," with the drug semaglutide. The researchers aim to determine if adding semaglutide, which regulates blood sugar in type 2 diabetes, can simplify meal planning without compromising blood sugar control. Individuals with type 1 diabetes for at least a year and who have used an automated insulin system for at least three months may qualify for this trial. Participants will receive either semaglutide or a placebo alongside their existing insulin therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in diabetes care.

Will I have to stop taking my current medications?

The trial requires that you stop using GLP1-RAs (a type of diabetes medication) at least 4 weeks before starting and any other anti-hyperglycemic agents (except insulin) at least 2 weeks before starting. If you are currently using these medications, you will need to stop them before participating.

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

Research has shown that semaglutide is usually well-tolerated. In earlier studies, only 5.1% of patients stopped using it due to side effects. Serious side effects were rare, occurring in just 0.5% of patients. Additionally, semaglutide offers benefits beyond managing diabetes, aiding in weight loss and improving heart health. Although not officially approved for type 1 diabetes, some studies suggest it can help control blood sugar when used with insulin. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about semaglutide for treating Type 1 diabetes because it introduces a unique mechanism of action compared to standard insulin therapies. Most treatments focus on insulin delivery, but semaglutide is a GLP-1 receptor agonist that helps regulate blood sugar by reducing glucagon levels and increasing the body's feeling of fullness. This could mean less reliance on insulin and potentially better blood sugar control. Additionally, semaglutide is administered as a simple weekly injection, which may be more convenient than daily insulin shots, offering a promising new option for managing Type 1 diabetes.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

In this trial, participants will receive either weekly semaglutide injections or placebo injections, both alongside regular closed-loop insulin pump therapy. Research has shown that semaglutide, a medication commonly used for type 2 diabetes, may also benefit people with type 1 diabetes. In one study, more patients taking semaglutide achieved better blood sugar control compared to those on a placebo. Semaglutide increases a hormone called GLP-1, which helps lower blood sugar and may also reduce appetite. While similar drugs have been used for type 1 diabetes, semaglutide has demonstrated superior results in managing blood sugar. Additionally, semaglutide has been linked to benefits such as weight loss and a reduced risk of heart problems in people with diabetes. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Type 1 Diabetes who are interested in a new way to manage their condition without the need for detailed carbohydrate counting. Participants should be willing to use an 'artificial pancreas' system and receive weekly injections of either Semaglutide or a placebo.

Inclusion Criteria

I have used an advanced insulin delivery system for at least 3 months.

I have been diagnosed with Type 1 Diabetes for over a year.

I agree to use birth control during the trial.

Exclusion Criteria

I have not used GLP1-RAs in the last 4 weeks.

I haven't taken any diabetes medication other than insulin in the last 2 weeks.

Planned or ongoing pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two subsequent blinded drug interventions; one with semaglutide and the other with placebo, each including 4 meal strategies with a 3-week duration

24 weeks

Weekly visits for injections and monitoring

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 tests if adding weekly Semaglutide injections to an artificial pancreas system helps control blood sugar levels in Type 1 Diabetes patients, compared to using the system with a placebo. The goal is to simplify meal planning by eliminating carb counting.

How Is the Trial Designed?

Group I: Weekly semaglutide (Ozempic®) injections on regular closed-loop insulin pump therapy Experimental Treatment 1 Intervention

Semaglutide is a Glucagon-like peptide 1 (GLP-1) receptor agonist. It up regulates GLP-1, which reduces glucagon levels, increases satiety and - in some particular cases - increases insulin production. It will be subcutaneously injected weekly by participants at progressively increasing doses. Once the maximum tolerated dose is achieved, participants will begin the meal strategies.

Group II: Weekly placebo injections on regular closed-loop insulin pump therapy Active Control 1 Intervention

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Published Research Related to This Trial

In a study involving 10 subjects with type 1 diabetes, adjunctive therapy with exenatide significantly reduced postprandial hyperglycemia compared to insulin alone, highlighting its potential to improve diabetes management.

Exenatide also effectively suppressed glucagon levels, which is important for controlling blood sugar after meals, making it a promising option for enhancing the performance of closed-loop insulin delivery systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of glucagon-like peptide-1 analogue versus amylin as an adjuvant therapy in type 1 diabetes in a closed loop setting with ePID algorithm. Renukuntla, VS., Ramchandani, N., Trast, J., et al.[2021]

In a study of 217 patients with Type 2 diabetes, switching to the co-formulation of insulin degludec and insulin aspart (IDegAsp) resulted in significant reductions in HbA1c and glucose levels, indicating effective blood glucose regulation.

Patients switching from more complex insulin regimens to IDegAsp experienced a decrease in insulin doses and the number of injections required, which likely improved their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Experience of our Center in Patients Undergoing Insulin Degludec/ Insulin Aspart Co-formulation Therapy. Altay, FP., Farzaliyeva, A., İyidir, ÖT., et al.[2023]

A study involving 33 adults with type 1 diabetes showed that the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg) 100 U/mL and 200 U/mL are bioequivalent, meaning they can be used interchangeably without affecting efficacy.

Both formulations provided comparable glucose-lowering effects and were well tolerated, with no significant safety events reported, indicating their safety for use in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the steady-state pharmacokinetic and pharmacodynamic profiles of 100 and 200 U/mL formulations of ultra-long-acting insulin degludec. Korsatko, S., Deller, S., Koehler, G., 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]

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, 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 52-week study involving 731 patients with type 2 diabetes, oral semaglutide significantly reduced HbA1c levels and body weight compared to placebo, demonstrating its efficacy when added to insulin with or without metformin.

The most common side effect of oral semaglutide was nausea, which was mostly mild to moderate, indicating a safety profile similar to other glucagon-like peptide 1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Zinman, B., Aroda, VR., Buse, JB., et al.[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]

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]

In a study involving 186 adults with type 1 diabetes, insulin degludec (IDeg) combined with mealtime insulin aspart (IAsp) resulted in a slightly greater reduction in HbA1c levels compared to insulin detemir (IDet) with IAsp, although the difference was not statistically significant.

IDeg + IAsp was associated with significantly lower rates of nocturnal hypoglycemia compared to IDet + IAsp, suggesting it may be a safer option for managing blood sugar levels in Japanese patients with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of IDeg + IAsp versus IDet + IAsp in subjects with type 1 diabetes: subgroup analysis of Japanese subjects. Ono, Y., Nishida, T., Hyllested-Winge, J., et al.[2022]

Degludec, an ultra-long-acting basal insulin, is as effective as insulin glargine but significantly lowers the risk of nocturnal hypoglycaemia, making it a safer option for diabetes management.

Its flexible once-daily dosing allows for better adherence, especially for patients with unpredictable schedules, addressing common barriers to effective insulin treatment in both type 1 and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexibly timed once-daily dosing with degludec: a new ultra-long-acting basal insulin. Josse, RG., Woo, V.[2022]

Semaglutide, a GLP-1 receptor agonist, has been shown to improve glucose control in type 2 diabetes mellitus (T2DM) by enhancing insulin secretion and reducing gastric emptying, addressing common treatment issues like low efficacy and weight gain.

Clinical trials have demonstrated that semaglutide not only effectively manages blood sugar levels but also offers cardiovascular benefits, making it a promising option for T2DM patients, especially in special populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of semaglutide in the management of type 2 diabetes: design, development, and place in therapy. Gomez-Peralta, F., Abreu, C.[2020]

Citations

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Semaglutide in Adults with Type 1 Diabetes and Obesity Results: A significantly greater percentage of patients in the semaglutide group than in the placebo group achieved the primary composite outcome (36% vs. 0%; ...

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Two-Year Real-World Effectiveness of Semaglutide in Patients ... Conclusion: In this real-world study, continuous treatment with semaglutide 1.7 mg or 2.4 mg for 2 years was associated with a clinically ...

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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/s41591-024-03463-z

Subcutaneous weekly semaglutide with automated insulin ... Semaglutide has demonstrated glycemic, weight and cardiac benefits in those with and without type 2 diabetes (T2D). Although semaglutide has not ...

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Semaglutide - StatPearls - NCBI Bookshelf T2DM and reduction of major cardiovascular events: The SUSTAIN clinical trials have exhibited favorable outcomes in reducing hemoglobin A1C ( ...

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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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1056872725001175

Evaluating the effect of Semaglutide as add-on therapy ... Semaglutide improved glycemic stability and reduced glycemic risk in T1D. HbA1c declined with nearly a 50 % reduction in daily insulin dose.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06909006

NCT06909006 | Semaglutide Treatment in Type 1 Diabetes The goal of this clinical trial is to investigate the efficacy of semaglutide on body weight, insulin dose requirements and improvements in glucose control ...