Inverse Association Between Weight-loss Inducing Anti-hyperglycemic Agents and Multiple Sclerosis: Data Mining of the FDA Adverse Event Reporting System Database
Afsaneh Shirani1, Anne Cross2, Olaf Stuve3
1University of Nebraska Medical Center, 2Washington University School of Medicine, 3UT Southwestern Medical Center
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.