Abstract Details

Title Inverse Association Between Weight-loss Inducing Anti-hyperglycemic Agents and Multiple Sclerosis: Data Mining of the FDA Adverse Event Reporting System Database

Topic Multiple Sclerosis

Presentation(s) P11 - Poster Session 11 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-001

Objective To test the hypothesis that the use of weight-loss-inducing anti-hyperglycemic drugs are inversely associated with multiple sclerosis (MS) using real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Background Several studies have demonstrated that early childhood and adolescent obesity are risk factors for MS susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The FAERS database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.

Design/Methods We performed a disproportionality analysis of FAERS between the first quarter of 2004 and the third quarter of 2022 using the OpenVigil2.1-MedDRA-v24 software to identify associations between MS and weight-loss-inducing agents, including both FDA-approved drugs and commonly used off-label drugs. If a drug was associated with ≤5 drug-disease (MS) combinations, it was excluded from the analysis. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CI). An upper limit of the 95%CI ≤1 for the ROR signified an inverse association.

Results Inverse associations were found between MS and the following weight-loss-inducing drugs: metformin (ROR:0.387; 95%CI:0.340-0.440), semaglutide (ROR:0.238; 95%CI:0.132-0.429), dulaglutide (ROR:0.165; 95%CI:0.109-0.248), liraglutide (ROR:0.161; 95%CI:0.091-0.284), and empagliflozin (ROR:0.234; 95%CI: 0.146 - 0.377). No inverse associations were found for non-anti-diabetic agents such as phentermine (ROR:0.856; 95%CI 0.46-1.593), bupropion (ROR:1.198; 95%CI:1.052-1.365), topiramate (ROR:1.422; 95%CI:1.218-1.659), zonisamide (ROR:1.054; 95%CI:0.679-1.634), and amphetamine (ROR:1.494; 95%CI:1.224-1.825). An exception was naltrexone (ROR:0.556; 95%CI:0.384-0.806).

Conclusions An inverse association between MS and anti-diabetic weight-loss-inducing drugs, such as metformin (biguanide), empagliflozin (sodium-glucose cotransporter-2 inhibitor), as well as semaglutide, dulaglutide, and liraglutide (glucagon-like peptide-1 receptor agonists) suggests the potential for repurposing these medications for MS.

Authors/Disclosures
Afsaneh Shirani, MD, FAAN PRESENTER	Dr. Shirani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics.
Anne H. Cross, MD, FAAN (Washington University School of Medicine)	Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech / F. Hoffman la Roche. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb . Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Cross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Consortium of MS Centers. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Cross has received research support from Genentech. Dr. Cross has received intellectual property interests from a discovery or technology relating to health care.
Olaf Stuve, MD, PhD, FAAN (UT Southwestern Medical Center)	Dr. Stuve has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Stuve has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Stuve has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Therapeutic Advances in Neurological Diseases. Dr. Stuve has received research support from US Department of Veterans Affairs. Dr. Stuve has received research support from National Multiple Sclerosis Society (US). Dr. Stuve has received research support from Merck KGaA.

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