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

Trial Summary

What is the purpose of this trial?

A closed-loop insulin system, often labelled the "artificial pancreas" (AP), consists of an insulin pump, a continuous glucose monitor, and an interface coordinating between them to regulate insulin dosage based on glucose levels. Primarily designed for managing type 1 diabetes, this system has demonstrated significant benefits in previous studies. Yet, despite these advantages, certain challenges persist. Semaglutide, utilized in treating type 2 diabetes and obesity, is a once-weekly injectable medication that elevates levels of a gastrointestinal hormone known as Glucagon-Like Peptide-1 (GLP-1). This hormone alters gastric emptying, inhibits glucagon release, and reduces appetite. While not officially sanctioned for type 1 diabetes treatment in North America, studies have explored its efficacy as an adjunctive therapy alongside insulin, yielding favorable outcomes in blood glucose regulation. Comparable drugs like liraglutide and exenatide have been employed in type 1 diabetes treatment as well, albeit with less pronounced glucose-regulating effects compared to semaglutide, even in type 2 diabetes. The goal of this 50-week randomized placebo-controlled crossover 2x4 factorial designed trial is to assess whether commercial automated insulin delivery (AID) systems using rapid-acting insulin with adjunct weekly injections of semaglutide (at the maximally tolerated dose) can replace carbohydrate counting with simple meal announcements (SMA) without degrading glucose control.

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.

What data supports the effectiveness of the drug semaglutide for type 1 diabetes?

Semaglutide has been shown to effectively lower blood sugar levels and body weight in people with type 2 diabetes, which suggests it might help manage blood sugar in type 1 diabetes as well. It works by stimulating insulin release, which is crucial for controlling blood sugar. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used in treatments like Rybelsus and Ozempic, has been tested in many patients with type 2 diabetes and is generally considered safe. It has a safety profile similar to other drugs in its class and has been shown to be safe for the heart in high-risk patients. ^{1 3 4 6 7}

How does the drug Semaglutide + Automated Insulin System differ from other treatments for type 1 diabetes?

This treatment combines semaglutide, a drug that mimics a hormone to help control blood sugar, with an automated insulin delivery system, offering a novel approach by potentially improving blood sugar control more effectively than insulin alone. Unlike traditional insulin therapies, this combination may help reduce post-meal blood sugar spikes by suppressing glucagon, a hormone that raises blood sugar levels. ^{8 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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 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]

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]

References

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

Semaglutide: First Global Approval. [2019]

2. United States 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. [2022]

3. Belgium pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

Profile of semaglutide in the management of type 2 diabetes: design, development, and place in therapy. [2020]

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

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

7. 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]

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

A comparison of IDeg + IAsp versus IDet + IAsp in subjects with type 1 diabetes: subgroup analysis of Japanese subjects. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. United States 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. [2021]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Experience of our Center in Patients Undergoing Insulin Degludec/ Insulin Aspart Co-formulation Therapy. [2023]

12. New Zealand 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. [2022]