Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis

The goal of this clinical trial is to evaluate if the study drug will reduce brain and retinal atrophy by reducing inflammation and subsequently slowing neurodegeneration in people with Multiple Sclerosis. The main outcome for the trial is change in normalized brain parenchymal volume (nBPV), measured by magnetic resonance imaging (MRI). Researchers will compare outcomes from participants randomized to the study drug, versus participants randomized to placebo, to see if there are signs of slowed neurodegeneration (i.e., reduction in brain and retinal atrophy).

Inclusion Criteria: * Diagnosis of MS (2024 criteria); clinically stable on MS therapy for ≥12 months without relapse or new lesions on brain MRI * Aged 18-60 years * Body mass index ≥27.0 kg/m2 Exclusion Criteria: * No GLP-1RA or GIP/GLP-1 RA in past year; no known hypersensitivity to medication class * No known Barrett's esophagus/gastroesophageal reflux disease, pancreatitis (including past), or gastroparesis * No personal/family history of medullary thyroid carcinoma or history of multiple endocrine neoplasia syndrome type 2 * No chronic kidney disease (estimated glomerular filtration rate ≤50 mL/min) in past year, type 1 diabetes, known diabetic retinopathy, use of insulin or insulin-inducing medications\*, dipeptidyl peptidase IV inhibitors\*\*, or warfarin; current/active alcohol or illicit substance abuse * No concerns about candidacy of individual on part of person's neurologist or study team clinicians * Current or planned (next 2 years) pregnancy/breastfeeding; if able to become pregnant, agree to reliable contraception (contraception requirements as discussed below)\*\*\* * currently-approved: Lispro, Aspart, Glulisine, Afrezza, Regular, Concentrated Regular, or Novolin, Velosulin, NPH, glargine, detemir, degludec, and premixed; approved secretagogues: sulphonylureas (e.g. glipizide (± metformin), glyburide (± metformin), glimepiride, pioglitazone/glimepiride) \& meglitinide analogues (nateglinide and repaglinide); \*\* currently-approved:sitagliptin, saxagliptin, linagliptin, alogliptin \*\*\*Contraception: Participants of childbearing potential (participant has a uterus and is pre-menopausal) must agree to use contraception, using either one method with a failure rate of \