Weekly Subcutaneous Semaglutide as Adjunct to Closed-loop Therapy in Type 1 Diabetes Care (SEMA-AP)

McGill University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Diabetes Mellitus, Type 1; Type 1 Diabetes

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05205928

2022-8097

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.**

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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28 participants in 2 patient groups

Placebo + closed-loop insulin system

Active Comparator group

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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