Inclusion Criteria:
- Age 18-30 years with T1D whose BMI meets FDA approval criteria for anti-obesity pharmacotherapy (BMI ≥30 kg/m2 alone or BMI ≥27 kg/m2 with a weight-related comorbidity)
- Clinical diagnosis of T1D
- Diabetes duration diagnosed ≥ 12 months ago
- HbA1c ≤10% at screening and within the past 90 days
- Stable reported insulin dosing in the past 90 days (within 15%)
- Stable reported BMI in the past 90 days (within 5%)
- Ability to provide written informed consent before any trial-related activities
- Use of real-time continuous glucose monitoring and planned continued use
- Females and males of childbearing potential willing to use highly effective methods of contraception for at least 1 month prior to randomization and agreement to use such a method during study participation and for 2 months after the last dose of study medication administration: Combined estrogen-progestogen contraception including: oral, intravaginal, transdermal (patch), Progestogen-only contraception: oral, injectable or implantable, Placement of an intrauterine device or intrauterine system, Bilateral tubal occlusion (fallopian tubes are blocked), Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate), or Complete sexual abstinence from male-female sex)
- Stated willingness to comply with all study procedures, medication regimen, and availability for the duration of the study
- Participants cannot be randomized if any laboratory safety parameter at screening is outside the below extended laboratory ranges. For randomization, participants should have
1. Creatinine <1.0mg
2. Triglycerides (<400 mg/dl)
3. ALT <3.5 times the upper normal limit (UNL)
Exclusion Criteria:
- Use of adjunctive diabetes therapies or anti-obesity medications (including any GLP-1 agonist) currently or within the past 6 months.
- Insulin dosing <0.5 units/kg/day
- Current psychiatric conditions impacting weight, including known eating disorders
- Contraindications to study medications, including:
- Personal history of pancreatitis, renal impairment, or known liver disease other than non-alcoholic hepatic steatosis
- Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Type 2
- Known or suspected allergy to semaglutide, excipients, or related products.
- Use of lipid lowering medications other than statins and omega-3 products
- Previous randomization in this trial. Participants who enrolled but did not randomize can be re-screened. Potential reasons for enrolment without randomization include scheduling conflicts for the baseline studies, or for females, not yet meeting the highly effective methods of contraception criteria.
- Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
- Diabetic ketoacidosis in the past 6 months
- Not meeting MRI safety criteria or claustrophobia preventing participation in the MRI
- Anemia or known hematologic condition impacting HbA1c reading, or another medical condition that precludes participation.
- Treatment with another investigational drug or other intervention within the past 1 month
- Subjects with a PHQ-9 score >15 or those found to have a lifetime history of suicide attempts, or suicidal ideation within the past 3 months on the C-SSRS
- Corn allergy
- Subjects with severe hypoglycemia requiring hospitalization in the past 3 months
- Clinically significant gastroparesis