Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

Abstract

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine-topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs 'drug abuse', 'drug withdrawal syndrome', 'prescription drug used without a prescription', and 'intentional product use issue' were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Keywords: drug abuse; drug misuse; glucagon-like peptide-1 (GLP-1) agonists; image- and performance-enhancing drugs (IPEDs); pharmacovigilance; semaglutide.

Figure 1

Number of adverse event reports (AERs) involving semaglutide, other glucagon-like peptide-1 (GLP-1) analogues (dulaglutide, liraglutide, exenatide, lixisenatide, tirzepatide, and albiglutide), and the combination phentermine–topiramate. Data source: Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS; 2018–2022). Legend: semaglutide: blue color; other GLP-1 analogues: orange; phentermine–topiramate: grey.