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

NCT05205928 | Completed Phase 2 DMC

• 1 other identifier: 2022-8097
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Keywords

Insulin; Closed-loop system; GLP-1 receptor agonist; Semaglutide; Artificial Pancreas; Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• Percentage of time of plasma glucose levels spent in target range (semaglutide vs placebo)

  Target range is defined to be between 3.9 and 10.0 mmol/L of placebo on closed-loop system vs semaglutide (at maximal tolerated dose) on closed-loop insulin system.

  4 weeks

Secondary Outcomes (15)

• Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L

  4 weeks

• Percentage of time spent in the following ranges of glucose levels: below 3.9 and 3.0 mmol/L

  4 weeks

• Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, and 13.9 mmol/L

  4 weeks

• Mean glucose level

  4 weeks

• Standard deviation of glucose levels as a measure of glucose variability

  4 weeks

Study Arms (2)

Placebo + closed-loop insulin system

ACTIVE COMPARATOR

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

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.

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

Interventions

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• Current or \< 2 week use of another GLP1-receptor agonist
• Less than 2 weeks use of any anti-hyperglycemic agent other than insulin
• Planned or ongoing pregnancy
• Breastfeeding individuals
• 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
• Severe diabetic ketoacidosis (DKA) within the last 6 months ("severe" referring to need to present to medical attention and requirement of intravenous insulin)
• Prior 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 eGFR \<15 mL/min/1.73 m2 (using CKD-EPI formula), measured within the last 12 months
• Clinically significant diabetic retinopathy or gastroparesis, as per the clinical judgment of the investigator
• History of bariatric surgery within 6 months of screening
• 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)
• Prior adverse reaction to GLP1-RAs
• Body mass index ≤ 21 kg/m2
• Regular use of hydroxyurea during the expected time of Dexcom G6 use, as this medication is known to cause inaccurate measurements (43)

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Research Institute of the McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (2)

• Pasqua MR, Doumat J, Tsoukas MA, Haidar A. Semaglutide Use With Automated Insulin Delivery in Adults With Type 1 Diabetes: Qualitative Analyses and Patient-reported Outcomes From a Randomized Controlled Trial. Can J Diabetes. 2025 Oct 30:S1499-2671(25)00367-3. doi: 10.1016/j.jcjd.2025.10.175. Online ahead of print.

  PMID: 41175929 DERIVED

• 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.

  PMID: 39794615 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Endocrinology & Metabolism

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: January 25, 2022
• Study Start: October 2, 2022
• Primary Completion: April 15, 2024
• Study Completion: June 30, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CA (1)