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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
28
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.
Research Institute of the McGill University Health Centre
Montreal, Quebec, Canada
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.
Time frame: 4 weeks
Percentage of time spent in the following ranges of glucose levels between 3.9 and 7.8 mmol/L
% as per CGM data
Time frame: 4 weeks
Percentage of time spent in the following ranges of glucose levels: below 3.9 and 3.0 mmol/L
% as per CGM data
Time frame: 4 weeks
Percentage of time spent in the following ranges of glucose levels: above 7.8, 10, and 13.9 mmol/L
% as per CGM data
Time frame: 4 weeks
Mean glucose level
Defined as per CGM data, in mmol/L
Time frame: 4 weeks
Standard deviation of glucose levels as a measure of glucose variability
Defined as per CGM data, in mmol/L
Time frame: 4 weeks
Percentage coefficient of variation of glucose levels
% as per CGM data
Time frame: 4 weeks
Proportion of participants with TIR between 3.9 - 10.0 mol/L ≥ 70%
As per CGM data
Time frame: 4 weeks
Glycated hemoglobin
Blood test to assess control within last 3-4 months
Time frame: 15 weeks
Average scores between interventions based on quality of life questionnaires
These include: Type 1 Diabetes Distress Scale, Hypoglycemic Fear Survey - II, INSPIRE questionnaire for adults, Diabetes Bowel Syndrome Questionnaire, Diabetes Treatment Satisfaction Questionnaire
Time frame: 15 weeks
Blood pressure and heart rate
Body measurements as described (mmHg and beats per minutes)
Time frame: 15 weeks
Measured of body mass: weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio
Measurements done at visit - weight in kilograms, body mass index as per kg/m\^2, circumferences in cm
Time frame: 15 weeks
Lipid profile, specifically: LDL-cholesterol, HDL-cholesterol, triglycerides
Blood tests, in mmol/L
Time frame: 15 weeks
Biochemical analyses (exploratory)
CRP, ferritin, IL-6, Brain natriuretic peptide, TXNIP
Time frame: 15 weeks
Urine albumin-creatinine ratio
Urine test
Time frame: 15 weeks
Glucagon, C-peptide, Paracetamol absorption after mixed meal tolerance test (in first 15 participants)
Test done where beverage given and subsequent blood tests done after.
Time frame: 15 weeks
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