SAN DIEGO — GLP-1s were safe for weight management in patients with multiple sclerosis (MS) but offered no significant protective benefit against disability or disease progression in a new study.

A small retrospective analysis of 131 adults with relapsing-remitting MS and secondary progressive MS who were taking a GLP-1 showed that the average BMI decreased by about 4 over a mean treatment period of 29 months. The average weight loss was 11.3 kg (25 pounds) during the same timeframe.

Earlier research had suggested GLP-1s may have neuroprotective effects in MS and other neurologic disorders. No such benefit was found in the new study. However, investigators cautioned that the jury is still out on whether the popular weight-loss drugs are effective as therapy for MS.

“So far, all we can say is that GLP-1s are generally safe in patients with MS. It’s far too early to say whether or not there is a biological benefit for MS pathophysiology and/or symptoms,” lead investigator Rachel Rodin, MD, PhD, neurologist and clinical fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told Medscape Medical News.

The findings were presented on February 6 at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026.

Evolving Research on GLP-1s in MS

Obesity is common in people with MS and can worsen disease activity, progression, and quality of life. Despite a scarcity of safety data in this patient population, the use of GLP-1s has increased in patients with MS.

Results from preclinical and small retrospective studies have suggested GLP-1s could slow MS disease progression and improve patient-reported outcomes.

“Many patients at my hospital’s MS center have been reporting that they feel better after starting a GLP-1. Anecdotally, patients have noted improved fatigue, cognition, and mobility,” Rodin said.

To study the issue further, researchers assessed the safety and clinical impact of GLP-1s in a single-center retrospective analysis of 131 patients with MS (mean age, 53 years; 82% women; 85% White). Two thirds of patients had relapsing-remitting MS and 25% had secondary progressive MS.

Participants received a GLP-1 between 2015 and 2025 and had MS clinic visits within 1 year before and at least 1 month after treatment initiation.

Semaglutide was the most commonly used (31%), followed by tirzepatide (11%) and dulaglutide (9%). Nearly half of patients (45%) took two or more GLP-1s over the study period due to insurance coverage changes, weight plateaus, or side effects.

Researchers compared BMI, Expanded Disability Status Scale (EDSS), and timed 25-foot walk (T25FW) scores before and after treatment using paired statistical analyses. The mean BMI at baseline was 36.9, and the mean EDSS score was 3.1.

Surprising Findings

The majority of patients (65%) showed no change to EDSS or T25FW scores. EDSS scores fell by 0.5-2.0 points in 17% of patients and increased by 0.5-4.0 points in 18% of patients, although these changes were not statistically significant.

Clinical relapses occurred in 7% of patients while on a GLP-1 receptor agonists, and 5% of patients acquired new or enlarging T2 lesions on MRI.

“We were surprised to see that there was no significant change in EDSS or timed 25-foot walk,” Rodin said.

Overall, GLP-1 therapy was well tolerated, although 42% of participants reported side effects, which researchers said is typical in non-MS users.

The most common side effects were constipation (13%), nausea (11%), and other gastrointestinal symptoms (4%). More serious adverse events included pancreatitis (1%), severe constipation requiring intervention (1%), and worsening MS-related fatigue or brain fog (1%), and dysesthesias (1%).

Two patients experienced dysesthesias described as a “sunburn sensation” that were ultimately attributed to their GLP-1 use. One patient had a seizure due to hypoglycemia, and one developed herpes simplex virus encephalitis, though this was believed to be unrelated to the GLP-1 medication.

More Studies Underway

Looking ahead, Rodin said the team plans to compare the study data with that of a retrospective control cohort to see if similar patients who did not receive GLP-1s experienced greater disease progression over the same period. They’ll also do a subgroup analysis, to determine if the drugs offer benefits in specific patient groups.

Rodin noted that future prospective studies should collect data on fatigue and cognition to determine if GLP-1s affect these symptoms in MS.

Also speaking at ACTRIMS Forum, Afsaneh Shirani, MD, associate director of neuroscience research and medical education at Saint Luke’s Marion Bloch Neuroscience Institute and clinical associate professor of neurology at the School of Medicine, University of Missouri-Kansas City, both in Kansas City, Missouri, noted that one potential issue is that GLP-1s don’t cross the blood-brain barrier.

“However, it is still possible that even these drugs might impact MS by changing the circulating metabolic profile of the blood and impacting the peripheral immune system and by interacting with the circumventricular organs in the brain,” Shirani said.

Preclinical evidence supports anti-inflammatory and neuroprotective effects, “but there is no strong evidence to suggest that they have any direct effect on limiting demyelination or promoting remyelination,” she added.

A randomized clinical trial into GLP-1s and MS has been planned at Johns Hopkins University, Shirani said, and should be launched soon.

Rodin reported having no relevant financial relationships. Shirani reported having a relationship with TG Therapeutics.