Weekly Subcutaneous Semaglutide as Adjunct to Closed-loop Therapy in Type 1 Diabetes Care

NCT ID: NCT05205928

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-02
• Study Completion Date: 2024-06-30

Brief Summary

A closed-loop insulin system, also referred to as the "artificial pancreas" (AP), is made up of an insulin pump, a continuous glucose monitor, and an application communicating between the two to adjust insulin administration based on glucose control. This is meant for the treatment of type 1 diabetes. The McGill Artificial Pancreas (MAP) has been used previously in type 1 diabetes with significant benefits. Though prior studies have shown significant benefit with this system, some challenges still exist.

Semaglutide is used in type 2 diabetes and obesity; it is a once-weekly injectable medication that increases levels of a gut hormone called Glucagon-Like Peptide-1, which modifies gastric emptying, suppresses glucagon, and suppresses appetite. Though its use is not approved in type 1 diabetes in North America, it (along with similar drugs) has been used in studies as adjunctive therapy with insulin with benefits on blood sugar control. Similar medications have been used in type 1 diabetes (such as liraglutide and exenatide), but are not as strong in glucose effect even in type 2 diabetes as compared with semaglutide.

The purpose of our study is to see if semaglutide administered weekly at the maximum tolerated dose in those with type 1 diabetes will have improved glucose control (as per time in target range from continuous glucose monitoring data) compared to placebo, while using a closed-loop insulin system.

Conditions

Type 1 Diabetes; Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo + closed-loop insulin system

Group Type: ACTIVE_COMPARATOR

Outpatient therapy: 11 weeks of drug therapy with usual treatment + 4 weeks of closed-loop therapy

Intervention Type: DRUG

The blinded drug will be used with participant's routine therapy (+ continuous glucose monitoring if not already in use) for 11 weeks with follow-up from qualified research personnel concerning pump settings, side effects, and incremental dose increase. While continuing to use the medication, there are 4 weeks of closed-loop pump therapy and drug use; glycemic outcomes will be taken from the last 4 weeks. This will be followed by laboratory and anthropometric testing, followed by 2 weeks of wash-out.

Semaglutide, Ozempic® (at maximum tolerated dose) + closed-loop insulin 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.

Group Type: EXPERIMENTAL

Outpatient therapy: 11 weeks of drug therapy with usual treatment + 4 weeks of closed-loop therapy

Intervention Type: DRUG

The blinded drug will be used with participant's routine therapy (+ continuous glucose monitoring if not already in use) for 11 weeks with follow-up from qualified research personnel concerning pump settings, side effects, and incremental dose increase. While continuing to use the medication, there are 4 weeks of closed-loop pump therapy and drug use; glycemic outcomes will be taken from the last 4 weeks. This will be followed by laboratory and anthropometric testing, followed by 2 weeks of wash-out.

Interventions

Outpatient therapy: 11 weeks of drug therapy with usual treatment + 4 weeks of closed-loop therapy

The blinded drug will be used with participant's routine therapy (+ continuous glucose monitoring if not already in use) for 11 weeks with follow-up from qualified research personnel concerning pump settings, side effects, and incremental dose increase. While continuing to use the medication, there are 4 weeks of closed-loop pump therapy and drug use; glycemic outcomes will be taken from the last 4 weeks. This will be followed by laboratory and anthropometric testing, followed by 2 weeks of wash-out.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• A clinical diagnosis of T1D for at least one year, as per their treating diabetes physician in agreement with the primary investigator's clinical judgment (confirmatory C-peptide and antibodies will not be required)
• Glycated hemoglobin (HbA1c) up to 11% (inclusive), performed within the last 6 months prior to study inclusion
• Insulin pump use (of any modality) for minimum 3 months
• Agreement to the use of highly effective method of birth control in persons of child-bearing age (if sexually active) and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche and have not reached menopause or have a disclosed medical condition causing sterility (e.g. hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.

Exclusion Criteria

1. Current or < 2 week use of another GLP1-receptor agonist

2. Less than 2 weeks use of any anti-hyperglycemic agent other than insulin

3. Planned or ongoing pregnancy

4. Breastfeeding individuals

5. Severe hypoglycemic episode within the last 3 months, defined as an event where glucose was < 4 mmol/L resulting in seizure, loss of consciousness, or need to present to the emergency department

6. Severe diabetic ketoacidosis (DKA) within the last 6 months ("severe" referring to need to present to medical attention and requirement of intravenous insulin)

7. Prior history of acute pancreatitis, chronic pancreatitis, or gallbladder disease

8. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2

9. Severe impairment of renal function with eGFR <15 mL/min/1.73 m2 (using CKD-EPI formula), measured within the last 12 months

10. Clinically significant diabetic retinopathy or gastroparesis, as per the clinical judgment of the investigator

11. History of bariatric surgery within 6 months of screening

12. Any serious medical or psychiatric illness likely to interfere with study participation as per the judgment of the investigator (e.g. cirrhosis, active cancer, decompensated schizophrenia)

13. Prior adverse reaction to GLP1-RAs

14. Body mass index ≤ 21 kg/m2

15. Regular use of hydroxyurea during the expected time of Dexcom G6 use, as this medication is known to cause inaccurate measurements (43)

16. Failure to comply to the study protocol and/or research group's recommendations (e.g. change in pump parameters, ketone measurement)

17. Inability or unwillingness to comply to safe diabetes management in the view of the study group (e.g. inappropriate treatment of hypoglycemia or lack thereof)

18. Any demonstrate of difficulty in using the iMAP system following training, as per investigator's judgment

19. Concern for safety of the participant, as per the clinical judgment of the primary investigator

**Note that for reasons of medicolegal protection for medical supervision, participants must be Canadian residents.**

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Michael Tsoukas

Assistant Professor, Endocrinology & Metabolism

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Research Institute of the McGill University Health Centre

Montreal, Quebec, Canada

Countries

Canada

References

Pasqua MR, Tsoukas MA, Kobayati A, Aboznadah W, Jafar A, Haidar A. Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial. Nat Med. 2025 Apr;31(4):1239-1245. doi: 10.1038/s41591-024-03463-z. Epub 2025 Jan 10.

Reference Type: DERIVED

PMID: 39794615 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2022-8097

Identifier Type: -

Identifier Source: org_study_id