Can an adult with multiple sclerosis use glucagon‑like peptide‑1 (GLP‑1) receptor agonists such as semaglutide or liraglutide for weight loss when lifestyle measures have failed and there are no contraindications?

GLP-1 Receptor Agonists for Weight Loss in Adults with Multiple Sclerosis

Yes, adults with multiple sclerosis can safely use GLP-1 receptor agonists such as semaglutide or liraglutide for weight loss when lifestyle measures have failed, with similar tolerability to the general population and measurable weight loss outcomes. 1, 2

Evidence from MS-Specific Studies

Two recent retrospective cohort studies directly examined GLP-1 receptor agonist use in people with MS, providing reassuring safety data:

• A 2025 U.S. single-institution study of 49 MS patients taking GLP-1 agonists for an average of 24.2 months showed that 29% experienced side effects with only 3 discontinuations due to tolerability—comparable to the general population 1
• Patients lost an average of 0.47 kg/month (1.03 lbs/month), with those having higher starting BMI losing more weight 1
• MS disease activity remained stable: only 4 patients developed new demyelinating lesions on MRI (most were either not on disease-modifying therapy or recently started on high-efficacy therapy) and one patient experienced a relapse 1
• A separate 2025 study confirmed GLP-1 medications are safe and effective in people with MS, showing decreased BMI (mean 3.7% loss) with no hospitalizations or deaths after initiation 2

Medication Selection and Efficacy

For maximum weight loss in MS patients, prioritize semaglutide 2.4 mg weekly (Wegovy) as first-line therapy:

• Semaglutide achieves 14.9% total body weight loss at 68 weeks, with 64.9% of patients achieving ≥10% weight loss 3, 4
• Tirzepatide 15 mg weekly demonstrates superior efficacy with 20.9% weight loss at 72 weeks, making it the preferred choice when maximum weight loss is the primary goal 3, 4
• Liraglutide 3.0 mg daily produces more modest weight loss of 5.24-6.1%, making it a third-line option 3, 4

The MS-specific data showed somewhat less weight loss than general population trials (0.47 kg/month vs. expected 1-2 kg/month), but weight loss was sustained and measurable. 1

Eligibility Criteria for MS Patients

Standard FDA-approved criteria apply to MS patients without modification:

• BMI ≥30 kg/m² qualifies without additional requirements 3, 4
• BMI ≥27 kg/m² qualifies with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea) 3, 4
• Must be combined with reduced-calorie diet (500-kcal deficit) and minimum 150 minutes/week of physical activity 3, 4

Absolute Contraindications

Do not prescribe GLP-1 receptor agonists in MS patients with:

• Personal or family history of medullary thyroid cancer 3, 4
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 3, 4
• History of severe hypersensitivity reaction to the medication 3

Dosing and Titration for Semaglutide

Follow standard titration schedule to minimize gastrointestinal side effects:

• Week 1-4: 0.25 mg weekly 3
• Week 5-8: 0.5 mg weekly 3
• Week 9-12: 1.0 mg weekly 3
• Week 13-16: 1.7 mg weekly 3
• Week 17+: 2.4 mg weekly (maintenance dose) 3

Slow titration every 4 weeks minimizes nausea, vomiting, and diarrhea, which occur in the majority of patients but are typically mild-to-moderate and transient. 3, 4

MS-Specific Monitoring Considerations

Monitor MS disease activity alongside standard weight loss parameters:

• Assess every 4 weeks during titration for gastrointestinal tolerance, weight loss progress, and blood pressure 3
• After reaching maintenance dose, monitor at least every 3 months for weight stability, cardiovascular risk factors, and medication adherence 3
• Continue routine MS monitoring with MRI and clinical assessments per standard MS care protocols 1, 2
• Evaluate treatment response at 12-16 weeks on maximum tolerated dose; discontinue if <5% weight loss after 3 months 3, 4

Additional Benefits for MS Patients

Beyond weight loss, GLP-1 receptor agonists may provide MS-relevant benefits:

• The 2025 MS cohort study showed increased vitamin D levels (mean increase of 8.1 ng/mL) after GLP-1 initiation, which is particularly relevant given vitamin D's role in MS 2
• Cardiovascular risk reduction: semaglutide reduces composite cardiovascular death, nonfatal MI, or nonfatal stroke by 20% (HR 0.80) in patients with established cardiovascular disease 3, 4
• Improved blood pressure, lipid profiles, and inflammatory markers 3

Common Pitfalls to Avoid

Do not delay initiation based solely on MS diagnosis—the evidence supports safety in this population. 1, 2

Do not discontinue disease-modifying therapy when starting GLP-1 receptor agonists—the MS-specific studies showed stable disease activity when patients remained on appropriate MS treatment. 1

Do not expect identical weight loss to general population trials—MS patients may lose weight more gradually (approximately 50% of expected rate), but weight loss is sustained. 1

Do not ignore gastrointestinal side effects—29% of MS patients experienced side effects, similar to the general population, and slow titration with dietary modifications (smaller meals, limiting alcohol and carbonated beverages) improves tolerability. 3, 1

Long-Term Use and Weight Maintenance

Counsel MS patients that lifelong treatment is necessary for sustained weight loss:

• Discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 3
• The MS-specific study showed sustained use for an average of 24.2 months with continued weight loss, supporting long-term safety 1
• Average wholesale price is approximately $1,619 per 30-day supply for semaglutide, requiring long-term financial planning 3

Interaction with MS Disease-Modifying Therapies

No drug interactions between GLP-1 receptor agonists and common MS disease-modifying therapies have been reported:

• The MS cohort study included patients on ocrelizumab (39%), various other DMTs, and 24% not on any DMT, with no safety signals 1
• GLP-1 receptor agonists delay gastric emptying and may affect absorption of oral medications, but this is not clinically significant for injectable MS therapies like ocrelizumab, natalizumab, or alemtuzumab 3, 5
• For oral MS therapies (fingolimod, dimethyl fumarate, teriflunomide), take GLP-1 receptor agonist and oral DMT at different times of day if absorption concerns arise 3