Semaglutide + Empagliflozin for Type 1 Diabetes

(SEMPA Trial)

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

Trial Summary

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.

What data supports the effectiveness of the drug combination Semaglutide and Empagliflozin for Type 1 Diabetes?

Research shows that Semaglutide and Empagliflozin are effective in managing blood sugar levels in people with Type 2 Diabetes. While this is not direct evidence for Type 1 Diabetes, it suggests potential benefits in controlling blood sugar. ^{1 2 3 4 5}

Is the combination of Semaglutide and Empagliflozin safe for humans?

Semaglutide is generally safe for humans, with most side effects being mild to moderate, such as stomach issues. It may increase the risk of gallbladder problems and should be used carefully in people with eye issues related to diabetes. Empagliflozin has been studied for safety in type 2 diabetes, but specific safety data for the combination with Semaglutide in type 1 diabetes is not available. ^{1 6 7 8 9}

How does the drug combination of Semaglutide and Empagliflozin differ from other treatments for Type 1 Diabetes?

The combination of Semaglutide and Empagliflozin is unique because it combines a glucagon-like peptide-1 (GLP-1) receptor agonist, which helps control blood sugar by enhancing insulin secretion, with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which lowers blood sugar by increasing glucose excretion through urine. This dual approach targets different mechanisms to improve blood sugar control, which is not typical in standard Type 1 Diabetes treatments. ^{1 2 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to learn if Empagliflozin and Semaglutide, individually and combined, added to Automated Insulin Delivery (AID) works to improve time-in-range in adults living with Type 1 Diabetes. It will also evaluate the safety of Empagliflozin and Semaglutide in this context. The primary hypothesis of this study is : - The combination therapy of semaglutide and empagliflozin will increase time-in-range compared to placebo when added to AID therapy. The secondary hypotheses are : * The combination therapy of semaglutide and empagliflozin will increase time-in-range compared to semaglutide alone when added to AID therapy. * The combination of semaglutide and empagliflozin will increase time-in-range compared to empagliflozin alone when added to AID therapy. In this study, the research team will compare Empagliflozin and Semaglutide to a placebo (a look-alike substance that contains no drug) to see if they improve time-in-range. This study has four groups: Group 1: semaglutide injection + empagliflozin tablet. Group 2: semaglutide injection + placebo tablet. Group 3: placebo injection + empagliflozin tablet. Group 4: placebo injection + placebo tablet. This is a 2x2 factorial crossover study. This means that all participants will undergo both injection intervention (placebo and semaglutide) arms. Within each injection arm, participants will take both tablets (placebo and empagliflozin). By the end of the study, every participant will have taken part in each study group.

Research Team

Dr. Michael Tsoukas

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

Dr. Melissa-Rosina Pasqua

Principal Investigator

Division of Endocrinology and Metabolism - McGill University Health Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

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

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. [2022]

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

Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. [2022]

3. England 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. [2022]

4. England 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. [2022]

5. United States 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. [2022]

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. [2022]

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

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. [2021]

10. England 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. [2022]

11. United States 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. [2020]

12. Germany 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. [2022]