Diabetes Type 1Phase 3SEMPANCT06894784
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 study testing Intervention Period 1: Semaglutide + Empagliflozin in people with Diabetes Type 1, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Type 1
- What is being tested?
- Intervention Period 1: Semaglutide + Empagliflozin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2025to Jan 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Research Institute of the McGill University Health Centre
Montreal, Quebec, H4A 3J1
Keddy Moise, BScHS, 438-531-6896, keddy.moise@affiliate.mcgill.ca
Dr. Ahmad Haidar, PhD, 514-398-4491, ahmad.haidar@mcgill.ca
About this study
Official title: Semaglutide And Empagliflozin Combination Therapy Added To Automated Insulin Delivery In Adults With Type 1 Diabetes (SEMPA)
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 :
Read more
- 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
- Diabetes Type 1
- Being tested
- Intervention Period 1: Semaglutide + Empagliflozin, Intervention Period 2: Semaglutide + Empagliflozin Placebo, Intervention Period 3: Semaglutide Placebo + Empagliflozin, Intervention Period 4: Semaglutide Placebo + Empagliflozin Placebo
- Keywords
- T1D, Combination Therapy, Automated Insulin Delivery, SGLT2-i, GLP1-RA, Insulin, Artificial Pancreas, GLP-1 receptor agonist, Diabetes Mellitus, Type 1
- Medical subject headings
- Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intervention Period 1: Semaglutide + EmpagliflozinDrug
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.
Intervention Period 2: Semaglutide + Empagliflozin PlaceboDrug
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.
Intervention Period 3: Semaglutide Placebo + EmpagliflozinDrug
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.
Intervention Period 4: Semaglutide Placebo + Empagliflozin PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system | Experimental | 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. Receives: 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 |
| Placebo + Automated Insulin Delivery system | Active comparator | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At the end of each intervention at weeks 16, 21, 29, 34
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study startApr 2025 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Diabetes Type 1Studies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 2×2 factorial, randomized, placebo-controlled, double-blind, crossover trial assessing the effects of Semaglutide and Empagliflozin, individually and combined, added to AID therapy.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Diabetes Canada
- Responsible party
- Principal investigator, Michael Tsoukas, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Dr. Michael Tsoukas, Principal investigator, Division of Endocrinology and Metabolism - McGill University Health CenterDr. Melissa-Rosina Pasqua, Study director, Division of Endocrinology and Metabolism - McGill University Health CenterDr. Vanessa Tardio, Study director, Division of Endocrinology and Metabolism - McGill University Health CenterDr. Ahmad Haidar, Study director, Department of Biomedical Engineering - McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06894784
- Sponsor's protocol ID
- 2025-10723
- Other IDs
- 2025
- Acronym
- SEMPA
- Status last verified
- Mar 2025
- First submitted
- 7 Mar 2025
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protocol will be included upon finalization onto the website, as well as upon request.
Publications
Cohen E, Tsoukas MA, von Oettingen JE, Yale JF, Garfield N, Vallis M, et al. A Randomized Controlled Trial to Alleviate Carbohydrate Counting in Type 1 Diabetes with Automated Fiasp and Pramlintide Closed-Loop Delivery. New Orleans: American Diabetes Association Conference; 2022.
Haidar A, Lovblom LE, Cardinez N, Gouchie-Provencher N, Orszag A, Tsoukas MA, Falappa CM, Jafar A, Ghanbari M, Eldelekli D, Rutkowski J, Yale JF, Perkins BA. Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 x 2 factorial randomized crossover trial. Nat Med. 2022 Jun;28(6):1269-1276. doi: 10.1038/s41591-022-01805-3. Epub 2022 May 12.
PubMed 35551290Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, Murphy HR, Nimri R, Norgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028. Epub 2019 Jun 8.
PubMed 31177185Bradley C. The diabetes treatment satisfaction questionnaire: DTSQ. Handbook of Psychology and Diabetes: a guide to psychological measurement in diabetes research and practice. 1994;111:132.
Fisher L, Hessler D, Polonsky W, Strycker L, Masharani U, Peters A. Diabetes distress in adults with type 1 diabetes: Prevalence, incidence and change over time. J Diabetes Complications. 2016 Aug;30(6):1123-8. doi: 10.1016/j.jdiacomp.2016.03.032. Epub 2016 Apr 4.
PubMed 27118163Nordisk N. Ozempic® Product Monograph. 2017.
Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, Thrasher J, Woo V, Philis-Tsimikas A. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 May;7(5):356-367. doi: 10.1016/S2213-8587(19)30066-X. Epub 2019 Mar 1.
PubMed 30833170Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014 Dec 20;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. Epub 2014 Sep 11.
PubMed 25220191de Wit HM, Vervoort GM, Jansen HJ, de Grauw WJ, de Galan BE, Tack CJ. Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT). Diabetologia. 2014 Sep;57(9):1812-9. doi: 10.1007/s00125-014-3302-0. Epub 2014 Jun 20.
PubMed 24947583Fakhoury WK, Lereun C, Wright D. A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes. Pharmacology. 2010;86(1):44-57. doi: 10.1159/000314690. Epub 2010 Jul 12.
PubMed 20616619Du Q, Wang YJ, Yang S, Zhao YY, Han P. Liraglutide for the treatment of type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials. Adv Ther. 2014 Nov;31(11):1182-95. doi: 10.1007/s12325-014-0164-2. Epub 2014 Nov 12.
PubMed 25388240Dejgaard TF, Schmidt S, Frandsen CS, Vistisen D, Madsbad S, Andersen HU, Norgaard K. Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial. Diabetes Obes Metab. 2020 Apr;22(4):492-500. doi: 10.1111/dom.13911. Epub 2019 Dec 19.
PubMed 31696598Ahren B, Hirsch IB, Pieber TR, Mathieu C, Gomez-Peralta F, Hansen TK, Philotheou A, Birch S, Christiansen E, Jensen TJ, Buse JB; ADJUNCT TWO Investigators. Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial. Diabetes Care. 2016 Oct;39(10):1693-701. doi: 10.2337/dc16-0690. Epub 2016 Aug 4.
PubMed 27493132Mathieu C, Zinman B, Hemmingsson JU, Woo V, Colman P, Christiansen E, Linder M, Bode B; ADJUNCT ONE Investigators. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care. 2016 Oct;39(10):1702-10. doi: 10.2337/dc16-0691. Epub 2016 Aug 9.
PubMed 27506222Johansen NJ, Dejgaard TF, Lund A, Schluntz C, Frandsen CS, Forman JL, Wewer Albrechtsen NJ, Holst JJ, Pedersen-Bjergaard U, Madsbad S, Vilsboll T, Andersen HU, Knop FK. Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Apr;8(4):313-324. doi: 10.1016/S2213-8587(20)30030-9. Epub 2020 Mar 2.
PubMed 32135138
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Semaglutide And Empagliflozin Combination Therapy Added To Automated Insulin Delivery In Adults With Type 1 Diabetes (SEMPA)
- ClinicalTrials.gov ID
- NCT06894784
- Acronym / sponsor ID
- SEMPA / 2025-10723
- Conditions
- Diabetes Type 1
- Keywords
- T1D, Combination Therapy, Automated Insulin Delivery, SGLT2-i, GLP1-RA, Insulin, Artificial Pancreas, GLP-1 receptor agonist
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- Diabetes Canada
- Study start
- Apr 2025 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 2×2 factorial, randomized, placebo-controlled, double-blind, crossover trial assessing the effects of Semaglutide and Empagliflozin, individually and combined, added to AID therapy.
| Arm | Type | Receives |
|---|---|---|
| Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system | Experimental | 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 PlaceboSemaglutide 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. |
| Placebo + Automated Insulin Delivery system | Active comparator | 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 PlaceboParticipants 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intervention Period 1: Semaglutide + EmpagliflozinSemaglutide 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. | Drug | Placebo + Automated Insulin Delivery system, Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system |
| Intervention Period 2: Semaglutide + Empagliflozin PlaceboSemaglutide 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. | Drug | Placebo + Automated Insulin Delivery system, Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system |
| Intervention Period 3: Semaglutide Placebo + EmpagliflozinSemaglutide 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. | Drug | Placebo + Automated Insulin Delivery system, Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system |
| Intervention Period 4: Semaglutide Placebo + Empagliflozin PlaceboSemaglutide 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. | Drug | Placebo + Automated Insulin Delivery system, Semaglutide, Ozempic® (at maximum tolerated dose) + Automated Insulin Delivery system |
Primary outcome
Time-in-Range
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
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.
12 secondary outcomes
Overall Time In Range
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Optimal Time In Range
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Hypoglycemia
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Mild Hyperglycemia
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time Above Range
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Time In Severe Hyperglycemia
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Total Insulin dose
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Basal insulin dose
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Bolus insulin dose
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Carbohydrate intake
Time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.
Patient-reported outcomes
Time frame: At the end of each intervention at weeks 16, 21, 29, 34
Patient-reported outcomes
Time frame: At the end of each intervention at weeks 16, 21, 29, 34
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- BackgroundCohen E, Tsoukas MA, von Oettingen JE, Yale JF, Garfield N, Vallis M, et al. A Randomized Controlled Trial to Alleviate Carbohydrate Counting in Type 1 Diabetes with Automated Fiasp and Pramlintide Closed-Loop Delivery. New Orleans: American Diabetes Association Conference; 2022.
- Background: PubMed 35551290Haidar A, Lovblom LE, Cardinez N, Gouchie-Provencher N, Orszag A, Tsoukas MA, Falappa CM, Jafar A, Ghanbari M, Eldelekli D, Rutkowski J, Yale JF, Perkins BA. Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 x 2 factorial randomized crossover trial. Nat Med. 2022 Jun;28(6):1269-1276. doi: 10.1038/s41591-022-01805-3. Epub 2022 May 12.
- Background: PubMed 31177185Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, Murphy HR, Nimri R, Norgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028. Epub 2019 Jun 8.
- BackgroundBradley C. The diabetes treatment satisfaction questionnaire: DTSQ. Handbook of Psychology and Diabetes: a guide to psychological measurement in diabetes research and practice. 1994;111:132.
- Background: PubMed 27118163Fisher L, Hessler D, Polonsky W, Strycker L, Masharani U, Peters A. Diabetes distress in adults with type 1 diabetes: Prevalence, incidence and change over time. J Diabetes Complications. 2016 Aug;30(6):1123-8. doi: 10.1016/j.jdiacomp.2016.03.032. Epub 2016 Apr 4.
- BackgroundNordisk N. Ozempic® Product Monograph. 2017.
- Background: PubMed 30833170Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, Thrasher J, Woo V, Philis-Tsimikas A. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 May;7(5):356-367. doi: 10.1016/S2213-8587(19)30066-X. Epub 2019 Mar 1.
- Background: PubMed 25220191Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014 Dec 20;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. Epub 2014 Sep 11.
- Background: PubMed 24947583de Wit HM, Vervoort GM, Jansen HJ, de Grauw WJ, de Galan BE, Tack CJ. Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT). Diabetologia. 2014 Sep;57(9):1812-9. doi: 10.1007/s00125-014-3302-0. Epub 2014 Jun 20.
- Background: PubMed 20616619Fakhoury WK, Lereun C, Wright D. A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes. Pharmacology. 2010;86(1):44-57. doi: 10.1159/000314690. Epub 2010 Jul 12.
- Background: PubMed 25388240Du Q, Wang YJ, Yang S, Zhao YY, Han P. Liraglutide for the treatment of type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials. Adv Ther. 2014 Nov;31(11):1182-95. doi: 10.1007/s12325-014-0164-2. Epub 2014 Nov 12.
- Background: PubMed 31696598Dejgaard TF, Schmidt S, Frandsen CS, Vistisen D, Madsbad S, Andersen HU, Norgaard K. Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial. Diabetes Obes Metab. 2020 Apr;22(4):492-500. doi: 10.1111/dom.13911. Epub 2019 Dec 19.
- Sizar O, Podder V, Talati R. Empagliflozin. In: StatPearls. StatPearls Publishing; 2024. Accessed April 15, 2024Link provided by the sponsor.
- Ozempic® Side Effects \| Ozempic® (semaglutide) injection. Accessed April 15, 2024Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Protocol will be included upon finalization onto the website, as well as upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intervention Period 1: Semaglutide + Empagliflozin in people with Diabetes Type 1, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Keddy Moise, BScHS (438-531-6896, keddy.moise@affiliate.mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-in-Range (time frame: At days 7, 35, 63 of the titration period and days 3 and 7 of each intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06894784, which also lists 36 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.