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

Chiappini, Stefania; Vickers‐Smith, Rachel; Harris, Daniel R.; Pelletier, G.; Corkery, John; Guirguis, Amira; Martinotti, Giovanni; Sensi, Stefano L.; Schifano, Fabrizio

doi:10.3390/ph16070994

Cited by 18 publications

(21 citation statements)

References 74 publications

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“…To identify the top 30 AEs with high reporting rates and robust signals, effective signals were ranked in descending order based on the number of AE reports and the lower limit of the 95% Confidence Interval (CI) for the ROR, as shown in Table 2 . Since the PRR values were equivalent to the ROR values, our signal strength analysis focused solely on comparing the ROR 95%CI lower limits ( Chiappini et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database

Li,

Zhang,

et al. 2024

Front. Pharmacol.

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Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application.Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA’s Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0.Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the “primary suspected” drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia—all documented on bendamustine’s label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug’s label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0–59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time.Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

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Section: Resultsmentioning

confidence: 99%

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database

Li,

Zhang,

et al. 2024

Front. Pharmacol.

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“…• Potentially serious side effects of these medications like thyroid cancer 38 • The risk of misuse by healthy nonobese people 39 • Effects on suicidality 40 • Costs for the health care systems 41 • Attempts to obtain these medications from non-licensed and unregulated agents 42 The most frequent adverse effects of GLP-1 receptor agonists are gastrointestinal symptoms such as decreased appetite, nausea, vomiting, burping, gastrointestinal pain, and constipation. 43 Pancreatitis and biliary disease may also occur.…”

Section: Side Effectsmentioning

confidence: 99%

“…47 An analysis of the FDA Adverse Events Reporting System found that there might indeed be a misuse/abuse potential of semaglutide as a higher proportion of reports were issued with regard to drug abuse, drug withdrawal syndrome, und drug use without a prescription compared with similar medications such as other GLP-1 receptor agonists or the combination of phentermine with topiramate. 39 In 2023, the European Medicines Agency started a review of suicidality associated with liraglutide and semaglutide. The review was triggered by the Icelandic Medicines Agency following reports of suicidal thoughts and self-injury in people using liraglutide and semaglutide.…”

Section: Side Effectsmentioning

confidence: 99%

“…The relative search volume for “Ozempic” on Google grew exponentially in the United States between March 2018 and February 2023 47 . An analysis of the FDA Adverse Events Reporting System found that there might indeed be a misuse/abuse potential of semaglutide as a higher proportion of reports were issued with regard to drug abuse, drug withdrawal syndrome, und drug use without a prescription compared with similar medications such as other GLP-1 receptor agonists or the combination of phentermine with topiramate 39 …”

Section: Side Effectsmentioning

confidence: 99%

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Glucagon-Like Peptide 1 Receptor Agonists in Psychiatry

Himmerich,

McElroy

2024

J Clin Psychopharmacol

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The glucagon-like peptide 1 (GLP-1)-based diabetes and obesity drug semaglutide with the trade names Ozempic™ and Wegovy™, respectively, which is produced by Novo Nordisk, will become the second best-selling drug in 2024 with estimated worldwide Ozempic™ sales of US ~$16 billion. 1 Finally, the pharmacological treatment of obesity seems to have a breakthrough after decades of setbacks as previous weight loss medications had to be withdrawn from the market because of serious side effects, eg, the cannbinoid-1 receptor antagonist rimonabant due to significant psychiatric adverse events, the selective serotonin-norepinephrine reuptake inhibitor sibutramine due to an increased incidence of nonfatal heart attacks and strokes, and serotonin receptor agonists fenfluramine and dexfenfluramine due to heart valve damage. Due to the increased demand and off-label use of semaglutide, governments have issued shortage alerts with appropriate supply not expected to return to normal until at least the end of 2024. 2 The explosive increase in prescriptions of GLP-1-based medications has raised hopes and concerns across the psychiatric community because weight loss, weight gain, and obesity often go along with psychiatric disorders, and they can be a consequence of psychiatric therapies. This editorial will briefly summarize the rise of GLP-1 agonists and the major hopes and concerns associated with this new class of medications. HOW GLP-1 RECEPTOR AGONISTS WORKGLP-1 is an intestinal peptide hormone that derives from posttranslational processing of proglucagon. GLP-1 is released in response to food intake and rapidly inactivated by the enzyme dipeptidyl peptidase IV (DPP-IV). GLP-1's actions may be transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. 3 GLP-1 stimulates insulin secretion but inhibits glucagon release, gastrointestinal motility, gastric emptying, appetite, and food intake. 3,4 As GLP-1 signaling boosts insulin secretion, GLP-1 receptor agonists have been tested for the treatment of type 2 diabetes (T2D). In April 2005, the first GLP-1 receptor agonist exenatide (also called exendin-4) was approved by the US Food and Drug Administration (FDA) for T2D. 5 Since then, the GLP-1 receptor agonists dulaglutide, liraglutide, lixisenatide, and semaglutide received FDA approval for T2D.When testing GLP-1 receptor agonists as T2D medication, it was observed that they also lead to weight loss, and thus, 2 of these GLP-1 receptor agonists, liraglutide and semaglutide, have been tested and approved for the treatment of obesity. Whereas liraglutide, which is metabolized by DPP-IVand neutral endopeptidase, required daily injections, semaglutide only needs to be injected once weekly. 6 Semaglutide became so popular that it caused a social media frenzy in 2022. It was reported in the press that celebrities used it as "skinny jab," which resulted in a global shortage of the drug, which is still ongoing. Meanwhile, semaglutide is even available as an oral tablet, 7 which boosted its popularity e...

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“…Recently, the increased demand for semaglutide and the possible misuse of these antidiabetics as a weight loss treatment in non-obese people have been described in the literature and by the media [ 6 , 7 , 8 ]. Almost simultaneously, reports of suicidal thoughts in people using liraglutide and semaglutide were highlighted [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database

Ruggiero,

Mascolo,

Spezzaferri

et al. 2024

Pharmaceuticals

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Background: A potential risk of suicide associated with liraglutide or semaglutide treatments has recently emerged. Therefore, we decided to investigate the reporting probability of suicidal events among glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A retrospective pharmacovigilance study of the European Pharmacovigilance database was conducted for the period from 1 January 2018 to 10 July 2023. Disproportionality analyses (reporting odds ratio, ROR) were performed to assess the reporting probability of suicidal events among GLP-1 RAs. Results: A total of 230 reports of suicidal events were identified. The most reported GLP-1 RA was liraglutide (38.3%), followed by semaglutide (36.5%) and dulaglutide (16.1%). The most reported events were suicidal ideation (65.3%) and suicide attempt (19.5%). Disproportionality analysis found a higher reporting probability of suicidal events for semaglutide than dulaglutide (ROR, 2.05; 95%CI, 1.40–3.01) and exenatide (ROR, 1.81; 95%CI, 1.08–3.05). In the same way, liraglutide was associated with a higher reporting probability of suicidal events than dulaglutide (ROR, 3.98; 95%CI, 2.73–5.82) and exenatide (ROR, 3.52; 95%CI, 2.10–5.92). On the contrary, a lower reporting probability was found for semaglutide than liraglutide (ROR, 0.51; 95%CI, 0.38–0.69). Conclusions: Suicidal events were mostly reported with semaglutide and liraglutide, which were also associated with significantly higher reporting probabilities compared to other GLP1 RAs. Although this study provides the reporting frequencies of suicide-related events with GLP-1 RAs, establishing causality requires further investigation, which will probably be addressed by the Pharmacovigilance Risk Assessment Committee of the European Medicine Agency in the future.

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

Cited by 18 publications

References 74 publications

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database

Glucagon-Like Peptide 1 Receptor Agonists in Psychiatry

Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database

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