Semaglutide + Empagliflozin for Type 1 Diabetes

(SEMPA Trial)

Recruiting at 1 trial location

Overseen By Keddy Moise, BScHS

Age: 18+

Sex: Any

Trial Phase: Phase 3

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

Must be taking: Automated insulin

Must not be taking: GLP1-RA, SGLT2i

Disqualifiers: Pregnancy, Pancreatitis, Renal impairment, others

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

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: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medications Empagliflozin (an SGLT2 inhibitor) and Semaglutide (a GLP-1 receptor agonist), alone or together, can help people with Type 1 Diabetes maintain healthier blood sugar levels when added to their insulin routine. Researchers are also assessing the safety of these medicines in this context. Participants will try different combinations of these medicines and a placebo to determine which works best. The trial seeks adults who have had Type 1 Diabetes for at least a year and currently use an automated insulin delivery system. 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 1 Diabetes.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking GLP1-RA medications at least one month before joining and SGLT2i medications at least two weeks before joining. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Research shows that using semaglutide with an Automated Insulin Delivery (AID) system can help adults with Type 1 diabetes control their blood sugar more effectively, potentially reducing their insulin needs. Studies also suggest that semaglutide can aid in blood sugar management and promote weight loss.

The FDA has already approved empagliflozin for treating Type 2 diabetes, indicating it has passed safety checks for that use. Research has shown that empagliflozin can lower blood sugar and reduce the risk of heart problems in people with diabetes.

Both treatments are generally well-tolerated. However, some individuals using semaglutide have experienced side effects such as nausea or digestive issues. Similarly, empagliflozin can sometimes cause dehydration or urinary tract infections. Individual reactions can vary.

This study tests both drugs together and separately to evaluate their effectiveness and safety when used with AID therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Semaglutide is unique because it is a Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist that enhances the body's satiety and reduces glucagon levels, potentially aiding in better blood sugar control for those with Type 1 Diabetes. Unlike standard insulin therapies, Semaglutide is administered as a once-weekly injection, which could mean fewer daily interventions for patients. Researchers are excited about this treatment because it offers a new mechanism of action by stimulating GLP-1, which might improve insulin secretion, providing an innovative way to manage Type 1 Diabetes alongside traditional insulin therapy.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research shows that semaglutide, which participants in this trial may receive, can help people with Type 1 Diabetes manage their blood sugar more effectively. Studies have found that semaglutide improves blood sugar control, reduces the need for insulin, and may lead to weight loss. It also stabilizes blood sugar levels, reducing extreme highs and lows.

For empagliflozin, research indicates it aids in blood sugar control by helping the body remove more sugar through urine, resulting in better overall blood sugar levels. Both semaglutide and empagliflozin have shown positive results individually, and researchers are now investigating if using them together could be even more effective. However, in this trial, participants will receive either semaglutide with an Automated Insulin Delivery system or a placebo with the same system to evaluate the effectiveness of semaglutide in this context. ^{1 3 4 5 6}

Who Is on the Research Team?

Dr. Michael Tsoukas

Principal Investigator

Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Melissa-Rosina Pasqua

Principal Investigator

Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Vanessa Tardio

Principal Investigator

Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Ahmad Haidar

Principal Investigator

Department of Biomedical Engineering - McGill University

Are You a Good Fit for This Trial?

Adults with Type 1 Diabetes are eligible for this trial. They'll be testing if adding two drugs, Semaglutide and Empagliflozin, to their insulin therapy helps control blood sugar better. Participants will try both drugs and placebos at different times.

Inclusion Criteria

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

Use of AID system for at least three months

Body Mass Index (BMI) ≥ 23 kg/m2

Exclusion Criteria

I have taken SGLT2 inhibitors within the last two weeks.

Breastfeeding

I have not used GLP1-RA drugs in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

A 12-week titration period for semaglutide to achieve a stable dose and minimize gastrointestinal side effects

12 weeks

Intervention

Participants undergo four 4-week intervention periods with different treatment combinations

16 weeks

Weekly visits for injections and tablets

Washout

Washout periods between treatment arms to eliminate carryover effects

2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Semaglutide

Trial Overview The study is testing the effectiveness of Semaglutide and Empagliflozin, alone and combined, on blood sugar control when added to Automated Insulin Delivery in Type 1 Diabetics. It's a crossover trial where everyone gets every treatment and placebo combination.

How Is the Trial Designed?

Group I: Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system Experimental Treatment 4 Interventions

Semaglutide is a Glucagon-Like Peptide 1 Receptor Agonist. It stimulates GLP1 in the body, which allows for increased satiety, reduced glucagon levels, delayed gastric emptying, and in some, increased insulin secretion. It is a once per week subcutaneous injection. Participants will self-administer the colourless solution subcutaneously in the abdomen, thighs, or upper arms once weekly per the dosing schedule below. Weeks 1-4 : 0.25 mg (0.19 mL) Weeks 5-8 : 0.50 mg (0.38 mL) Weeks 9-12 : 1.0 mg (0.74 mL) Weeks 13-22 : 1.0 mg (0.74 mL) To match the recommendation from the product monograph and to ensure a steady state is reached before initiating the evaluation period, study drugs will be titrated for 12 weeks.

Group II: Placebo + Automated Insulin Delivery system Active Control 4 Interventions

Participants will self-administer the colourless solution subcutaneously in the abdomen, thighs, or upper arms once weekly per the dosing schedule below. Weeks 1-4 : 0.19 mL Weeks 5-8 : 0.38 mL Weeks 9-12 : 0.74 mL Weeks 13-22 : 0.74 mL To match the recommendation from the product monograph and to ensure a steady state is reached before initiating the evaluation period, study drugs will be titrated for 12 weeks.

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+

Diabetes Canada

Collaborator

Trials

13

Recruited

1,200+

Published Research Related to This Trial

In the SUSTAIN 1 to 5 trials involving 3918 participants with type 2 diabetes, semaglutide significantly helped more individuals achieve their HbA1c targets (47% to 74%) compared to placebo (7% to 19%) and other active comparators (16% to 29%).

Semaglutide was effective in achieving these results while minimizing unwanted outcomes, such as weight gain, severe hypoglycaemia, and gastrointestinal side effects, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. DeVries, JH., Desouza, C., Bellary, S., et al.[2022]

In a phase 3 trial involving 388 treatment-naive patients with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.45% with 0.5 mg and 1.55% with 1.0 mg doses compared to placebo, indicating its efficacy in improving glycaemic control.

Semaglutide also led to significant weight loss, with reductions of 3.73 kg and 4.53 kg for the respective doses, while maintaining a safety profile similar to existing GLP-1 receptor agonists, with most adverse events being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Sorli, C., Harashima, SI., Tsoukas, GM., et al.[2022]

In a phase 3a trial involving 1089 participants, semaglutide significantly reduced HbA1c levels more than insulin glargine, achieving reductions of 1.21% and 1.64% for 0.5 mg and 1.0 mg doses, respectively, compared to 0.83% with insulin glargine.

Semaglutide also led to weight loss (3.47 kg and 5.17 kg for the two doses) while insulin glargine resulted in weight gain (1.15 kg), and semaglutide was associated with fewer hypoglycaemic episodes, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Aroda, VR., Bain, SC., Cariou, B., et al.[2022]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively lower hemoglobin A1c levels by approximately -1.5% and reduce body weight by about -4.5 kg in phase 3 trials, demonstrating comparable efficacy to dulaglutide.

While semaglutide offers cardiovascular benefits, including a reduced risk of major cardiovascular events, it is associated with an increased risk of retinopathy complications in patients with existing diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. Miles, KE., Kerr, JL.[2021]

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]

In a 52-week phase 4 trial involving Japanese patients with type 2 diabetes, empagliflozin as an add-on to liraglutide was well tolerated, with 59.4% to 66.7% of patients reporting at least one adverse event, indicating a manageable safety profile.

The combination therapy resulted in significant improvements in glycaemic control (reduction in HbA1c), body weight, and blood pressure, demonstrating its efficacy in enhancing diabetes management compared to liraglutide alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Empagliflozin as Add-On Therapy to GLP-1 Receptor Agonist (Liraglutide) in Japanese Patients with Type 2 Diabetes Mellitus: A Randomised, Double-Blind, Parallel-Group Phase 4 Study. Terauchi, Y., Utsunomiya, K., Yasui, A., et al.[2020]

In a 12-week trial involving 75 adults with type 2 diabetes, semaglutide significantly improved both first- and second-phase insulin secretion, indicating enhanced beta cell function.

Semaglutide also led to better glycaemic control, with reduced fasting and postprandial glucose levels, and was well tolerated by participants, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Kapitza, C., Dahl, K., Jacobsen, JB., et al.[2022]

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, a GLP-1 receptor agonist, significantly reduces HbA1c levels by up to 1.38% and also helps in reducing body weight and systolic blood pressure, making it an effective treatment for type 2 diabetes.

While semaglutide shows a good safety profile with no increased rates of hypoglycemia, it is associated with higher incidences of gastrointestinal side effects like nausea and vomiting, and further monitoring is needed for potential risks of pancreatitis and diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Andreadis, P., Karagiannis, T., Malandris, K., et al.[2022]

Semaglutide, a once-weekly GLP-1 receptor agonist, significantly reduced HbA1c levels, self-measured plasma glucose, fasting plasma glucose, and body weight in patients with type 2 diabetes mellitus (T2DM), based on a meta-analysis of 11 studies involving 9519 participants.

While semaglutide increased the incidence of adverse events slightly, it did not significantly raise the risk of serious adverse events or hypoglycemic events compared to control, indicating it is a safe and effective option for T2DM patients, especially those with obesity or poor adherence to daily medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of once-weekly glucagon-like peptide-1 receptor agonist semaglutide in patients with type 2 diabetes mellitus: a systemic review and meta-analysis. Li, X., Qie, S., Wang, X., et al.[2022]

Citations

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

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%; ...

2. nature.com nature.com/articles/s41591-024-03463-z

Subcutaneous weekly semaglutide with automated insulin ... In this trial, semaglutide improved glycemic control, with lower insulin requirements, in adults with T1D when used with AID. Semaglutide also ...

3. 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.

4. 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 ...

5. muhc.ca muhc.ca/news-and-patient-stories/news/semaglutide-known-ozempic-can-be-beneficial-people-type-1-diabetes

Semaglutide - known as Ozempic - can be beneficial to ... A first randomized clinical trial shows that semaglutide use in type 1 diabetes is associated with improved glucose management, weight loss and lower insulin ...

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.