RecruitingNCT06894784SEMPAUpdated Mar 30, 2025

A Clinical Trial to Evaluate The Effects of Semaglutide and Empagliflozin Combined to Automated Insulin Delivery on Diabetes Control in Adults Living With Type 1 Diabetes

A Phase 3 interventional study of Intervention Period 1: Semaglutide + Empagliflozin and Intervention Period 2: Semaglutide + Empagliflozin Placebo in Diabetes Type 1, sponsored by McGill University Health Centre/Research Institute of the McGill University Health Centre. Recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-30.

Sponsored by McGill University Health Centre/Research Institute of the McGill University Health Centre · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 36
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the detailed description

This study is designed as a 2x2 factorial, randomized, placebo-controlled, double-blind, crossover trial to investigate the effects of semaglutide and empagliflozin, individually and combined, on time-in-range (TIR) in adults with type 1 diabetes (T1D) using automated insulin delivery (AID) systems.

Study Design and Randomization:
Factorial Design: The 2x2 factorial design allows for the simultaneous assessment of two interventions (semaglutide and empagliflozin) and their interaction. This design efficiently explores the individual and combined effects of the drugs. Randomization: Participants will be randomized in a 1:1 ratio to determine the order of the semaglutide and placebo injections (Arm A: semaglutide first, Arm B: placebo first). Within each arm, the order of empagliflozin and placebo tablets will also be randomized 1:1. This ensures that any potential carryover effects are minimized. Double-Blind: Both participants and investigators will be blinded to the treatment assignments, minimizing bias in data collection and analysis. Crossover Design: Each participant will receive all four treatment combinations (semaglutide + empagliflozin, semaglutide + placebo, placebo + empagliflozin, placebo + placebo), allowing for within-subject comparisons and reducing inter-individual variability.
Study Procedures:
Screening and Baseline: Participants will undergo a screening visit to confirm eligibility criteria. Baseline characteristics, including demographic data, medical history, and current diabetes management, will be collected. Titration Period (Semaglutide): A 12-week titration period for semaglutide will be implemented to achieve a stable dose and minimize gastrointestinal side effects. This gradual dose escalation will follow standard clinical practice. Intervention Periods (Four Weeks Each): Each participant will undergo four four-week intervention periods, representing the four treatment combinations. During each intervention period, participants will continue to use their AID system.
Participants will receive daily injections (semaglutide or placebo) and daily tablets (empagliflozin or placebo) according to the randomization schedule. Washout Periods: A two to four-week washout period will be implemented between the semaglutide/placebo arms to eliminate any carryover effects of semaglutide. A one to seven-day washout period will be implemented between the empagliflozin/placebo tablet administrations. This short period is considered sufficient for the elimination of empagliflozin. CGM Data Collection:
Continuous glucose monitoring (CGM) data will be collected throughout the study, with a focus on the four-week intervention periods. CGM data will be used to calculate the primary outcome (TIR) and secondary outcomes. Questionnaires: At the end of each four-week intervention period, participants will complete questionnaires to assess: Diabetes distress and treatment satisfaction. Adverse Event Monitoring: Adverse events will be recorded throughout the study, from informed consent to the end of participation.
Statistical Analysis:
Intention-to-Treat (ITT) Analysis: Statistical analyses will be performed on an ITT basis, including all participants who were randomized. Factorial Analysis: The factorial design allows for the assessment of the main effects of semaglutide and empagliflozin, as well as their interaction. Mixed-Effects Models: Mixed-effects models will be used to account for repeated measures and within-subject variability. Descriptive Statistics: Descriptive statistics will be used to summarize baseline characteristics and outcome measures. Adverse Event Analysis: Adverse events will be summarized and analyzed for frequency and severity.
Safety Considerations:

Participants will be closely monitored for adverse events. Rescue medications will be available for hypoglycemic events. Participants will receive education on the safe use of semaglutide, empagliflozin, and the AID system. The investigators will have the right to remove any participant from the study at any time if they feel it is in the best interest of the participant.

Conditions studied

Diabetes Type 1

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Keywords

T1D
Combination Therapy
Automated Insulin Delivery
SGLT2-i
GLP1-RA
Insulin
Artificial Pancreas
GLP-1 receptor agonist
Diabetes Mellitus, Type 1

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's planned enrollment of 36 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre is the lead sponsor of 414 studies on the registry; 106 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

The inclusion criteria at the time of enrollment are:

Males and females aged 18 or older.
Clinical diagnosis of T1D for at least one year.
Use of AID system for at least three months.
Body Mass Index (BMI) ≥ 23 kg/m2.

The exclusion criteria are:

Use of GLP1-RA within one month of admission.
Use of SGLT2i within two weeks of admission.
Planned or ongoing pregnancy.
Breastfeeding.
Severe hypoglycemic episode within three months of admission (defined as an event where blood glucose levels were \< 4.0 mmol/L, resulting in seizure, loss of consciousness, or the need to present to the emergency department).
Diabetic ketoacidosis episode within six months of admission.
History of acute pancreatitis, chronic pancreatitis, or gallbladder disease.
Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
Severe impairment of renal function with an eGFR \< 30 mL/min/1.73 m2 within four months of admission. eGFR will be computed using the CKD-EPI method.
Clinically significant diabetic retinopathy or gastroparesis, as per the investigator's judgement.
Bariatric surgery within six months of admission.
A serious medical or psychiatric illness that would likely interfere with participation in this study, as per the investigator's judgement.
Inability or unwillingness to comply with safe diabetes management practices, as per the investigator's judgment.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial assignment
Masking: Double (Participant, Investigator)
Enrollment: 36 participants (estimated)

Study arms

Experimental
Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system
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.
Drug: Intervention Period 1: Semaglutide + Empagliflozin · Drug: Intervention Period 2: Semaglutide + Empagliflozin Placebo · Drug: Intervention Period 3: Semaglutide Placebo + Empagliflozin · Drug: Intervention Period 4: Semaglutide Placebo + Empagliflozin Placebo
Active comparator
Placebo + Automated Insulin Delivery system
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.
Drug: Intervention Period 1: Semaglutide + Empagliflozin · Drug: Intervention Period 2: Semaglutide + Empagliflozin Placebo · Drug: Intervention Period 3: Semaglutide Placebo + Empagliflozin · Drug: Intervention Period 4: Semaglutide Placebo + Empagliflozin Placebo

Interventions

DrugIntervention Period 1: Semaglutide + Empagliflozin
Semaglutide Injection: Subcutaneous injection, titrated over 12 weeks to a stable dose (1 mg), administered weekly. Empagliflozin Tablet: Oral tablet (2.5 mg), administered daily. Automated Insulin Delivery (AID) System: Continuous use of the participant's personal commercial AID system.
DrugIntervention Period 2: Semaglutide + Empagliflozin Placebo
Semaglutide Injection: Subcutaneous injection, titrated over 12 weeks to a stable dose (1 mg), administered weekly. Empagliflozin Placebo Tablet: Oral placebo tablet, matched in appearance to empagliflozin (2.5 mg), administered daily. Automated Insulin Delivery (AID) System: Continuous use of the participant's personal commercial AID system.
DrugIntervention Period 3: Semaglutide Placebo + Empagliflozin
Semaglutide Placebo Injection: Subcutaneous placebo injection (titrated over 12 weeks to a stable 1 mg dose), matched in appearance to semaglutide, administered weekly. Empagliflozin Tablet: Oral tablet (2.5 mg), administered daily. Automated Insulin Delivery (AID) System: Continuous use of the participant's personal commercial AID system.
DrugIntervention Period 4: Semaglutide Placebo + Empagliflozin Placebo
Semaglutide Placebo Injection: Subcutaneous placebo injection (titrated over 12 weeks to a stable 1 mg dose), matched in appearance to semaglutide, administered weekly. Empagliflozin Placebo Tablet: Oral placebo tablet (2.5 mg), matched in appearance to empagliflozin, administered daily. Automated Insulin Delivery (AID) System: Continuous use of the participant's personal commercial AID system.

What researchers measure

Primary outcomes

Time-in-Range
The percentage of time spent in target glucose range (3.9-10.0 mmol/L), between Semaglutide and Empagliflozin versus placebo, added to AID therapy.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.

Secondary outcomes

Overall Time In Range
Percentage of time (%) spent in ranges of glucose levels : between 3.9 to 10 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Optimal Time In Range
Percentage of time (%) spent in ranges of glucose levels : between 3.9 to 7.8 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Hypoglycemia
Percentage of time (%) spent in ranges of glucose levels : below 3.9 and 3.0 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Mild Hyperglycemia
Percentage of time (%) spent in ranges of glucose levels : above 7.8 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time Above Range
Percentage of time (%) spent in ranges of glucose levels : above 10 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Severe Hyperglycemia
Percentage of time (%) spent in ranges of glucose levels : above 13.9 mmol/L Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Total Insulin dose
Total daily insulin dose (U/l) Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Basal insulin dose
Total daily basal dose (U/l) Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Bolus insulin dose
Total daily bolus dose (U/l) Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Carbohydrate intake
Average daily meal carbohydrate intake (grams/day) Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Patient-reported outcomes
Average scores (unit) of the questionnaire : - Diabetes Distress Scale Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At the end of each intervention at weeks 16, 21, 29, 34
Patient-reported outcomes
Average scores (unit) of the questionnaire: - Diabetes Treatment Satisfaction Questionnaire Nota Bene: Secondary endpoints will be computed for (i) semaglutide and empagliflozin versus placebo, (ii) semaglutide and empagliflozin versus empagliflozin alone, (iii) semaglutide and empagliflozin versus semaglutide alone.
Time frame: At the end of each intervention at weeks 16, 21, 29, 34

Study locations

1 of 1 sites recruiting

Research Institute of the McGill University Health Centre
Montréal, Quebec H4A 3J1, Canada
- Keddy Moise, BScHS · Contact · keddy.moise@affiliate.mcgill.ca · 438-531-6896
- Dr. Ahmad Haidar, PhD · Contact · ahmad.haidar@mcgill.ca · 514-398-4491
- Dr. Michael Tsoukas, MD, FRCPC · Principal investigator
- Dr. Ahmad Haidar, PhD · Sub investigator
- Dr. Melissa-Rosina Pasqua, MD, FRCPC · Sub investigator
- Dr. Vanessa Tardio, MD, FRCPC · Sub investigator
Recruiting

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Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol. 1999 May;276(5):R1541-4. doi: 10.1152/ajpregu.1999.276.5.R1541. PubMed 10233049 ↗
Pasqua MR, Jafar A, Kobayati A, Tsoukas MA, Haidar A. Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial. Diabetes Care. 2023 Jan 1;46(1):165-172. doi: 10.2337/dc22-0490. PubMed 36331522 ↗
Haidar A, Yale JF, Lovblom LE, Cardinez N, Orszag A, Falappa CM, Gouchie-Provencher N, Tsoukas MA, El Fathi A, Rene J, Eldelekli D, Lanctot SO, Scarr D, Perkins BA. Reducing the need for carbohydrate counting in type 1 diabetes using closed-loop automated insulin delivery (artificial pancreas) and empagliflozin: A randomized, controlled, non-inferiority, crossover pilot trial. Diabetes Obes Metab. 2021 Jun;23(6):1272-1281. doi: 10.1111/dom.14335. Epub 2021 Feb 28. PubMed 33528904 ↗
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Individual participant data

Plan to share: Yes — Protocol will be included upon finalization onto the website, as well as upon request.

Supporting information: Study protocol

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT06894784
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators: Diabetes Canada
Responsible party: Michael Tsoukas (Assistant Professor of Medicine, Principal Investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre) — Principal investigator
First posted: Mar 25, 2025
Start date: Apr 2025 (estimated)
Primary completion: Jan 2027 (estimated)
Completion: Jan 2027 (estimated)
Last update: Mar 30, 2025

Study contacts

Keddy Moise, BScHS

Contact

keddy.moise@affiliate.mcgill.ca

438-531-6896

Dr. Ahmad Haidar

Contact

ahmad.haidar@mcgill.ca

514-398-4491

Dr. Michael Tsoukas

principal investigator · Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Melissa-Rosina Pasqua

study director · Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Vanessa Tardio

study director · Division of Endocrinology and Metabolism - McGill University Health Center

Dr. Ahmad Haidar

study director · Department of Biomedical Engineering - McGill University

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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Discussion

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