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.