More than 40% of young adults with type 1 diabetes (T1D) also have overweight or obesity. Each of these diagnoses increase the risk of adverse cardiovascular events. GLP-1 analogues are anti-obesity medications that are cardioprotective in adults with type 2 diabetes, however evaluation of these agents in people with T1D has been limited to glycemic outcomes. Investigators aim to study the impact of GLP-1 analogue obesity treatment on markers of cardiometabolic risk in young adults with T1D and obesity.
This proposal will address critical knowledge gaps of understanding potential salutary effects of GLP-1 analogue anti-obesity treatment with weekly semaglutide 2.4 mg on cardiometabolic risk factors in young adults with T1D and obesity, the group of people with T1D at greatest risk for future cardiovascular disease. Investigators aim to examine the impact of 12 months of treatment with weekly semaglutide 2.4 mg compared to placebo on abdominal adipose tissue distribution, glucose metabolism and postprandial atherosclerotic lipoproteins in young people with T1D and obesity. This is a single-center, parallel group, double-blinded, placebo controlled, randomized clinical trial. After informed consent procedures, participants will complete four assessments: 1) Abdominal MRI to evaluate abdominal adipose partitioning, 2) Euglycemic hyperinsulinemic clamp with isotope tracer enhancement to evaluate gluconeogenesis and glucose, glycerol, and b-hydroxybutyrate turnover to assess measures of insulin resistance, 3) DEXA scan to evaluate total body composition, and 4) a High-fat mixed meal tolerance test to evaluate postprandial lipemia. After completing these baseline measures, participants will be randomized in a 2:1 ratio to receive weekly injected semaglutide (escalated to 2.4 mg or maximum tolerated dose) or placebo to treat obesity for 52 weeks. At 52 weeks, participants will repeat the baseline tests. They will then complete a wean off of study drug (up to 4 weeks) and 2 weeks of additional monitoring for insulin titration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
54
Escalated to 2.4mg or max tolerated dose
Matched placebo.
Yale Pediatric Diabetes Center, Adult and Children's Progam
New Haven, Connecticut, United States
RECRUITINGChange in VAT/(VAT+SAT) from baseline to 12 months
Measured as VAT/Subcutaneous Adipose Tissue + VAT changes over 1 year.
Time frame: baseline and 12 months
Change in hepatic insulin resistance from baseline to 12 months
Hepatic insulin resistance, measured by serum concentration of beta-hydroxybutyrate (surrogate marker of acetyl-CoA, which regulates gluconeogenesis), changes over 1 year.
Time frame: baseline and 12 months
Change in triglycerides from baseline to 12 months
Change in triglycerides after a high-fat mixed meal tolerance test, expressed as the total Area Under the Curve (AUCTG) over 6 hours from baseline to 1 year.
Time frame: baseline and 12 months
Change in weight from baseline to 12 months
Mean change in weight (kilograms) assessed using a scale
Time frame: baseline and 12 months
Change in percent body fat from baseline to 12 months
Mean change in percent body fat assessed using DEXA scan measurements
Time frame: baseline and 12 months
Change in BMI from baseline to 12 months
Mean change in BMI calculated using measured height and weight.
Time frame: baseline and 12 months
Change in mean glucose concentration
Change in mean glucose concentration. Data collected as available using participant's personal clinical continuous glucose monitor.
Time frame: baseline and 12 months
Mean time in normal glucose range
Mean time in normal glucose range. Range=70-180 mg/dl and 3.9-10 mmol/L. Data collected as available using participant's personal clinical continuous glucose monitor.
Time frame: baseline and 12 months
Mean time in level 1 and 2 hyperglycemia, high range
Mean time in level 1 and 2 hyperglycemia. Range= \>180, \>250 mg/dL and \>10, \>13.9 mmol/L. Data collected as available using participant's personal clinical continuous glucose monitor.
Time frame: baseline and 12 months
Mean time in level 1 and 2 hyperglycemia, low range
Mean time in level 1 and 2 hyperglycemia. Range= \<70, \<54 mg/dL and \<3.9, \<3.0 mmol/L. Data collected as available using participant's personal clinical continuous glucose monitor.
Time frame: baseline and 12 months
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