(C-180) Review of Depression Signal Discovered Following Spontaneous Reports of Injectable Anti Diabetics (Semaglutide and Tirzepatide)

Background: Semaglutide and Tirzepatide are a type 2 diabetes drugs that acts as a glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide have a dual anti diabetic action through a second mechanism which is glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. Both medications with diet and exercise helps in improving glycemic control in adults. At the Saudi Food and Drug Authority (SFDA) we received through our spontaneous reporting vigilance system couple of cases reporting depression after using these drugs. At that point of time, neither of the drugs have mentioned that risk in the reference safety information and that’s where the signal detection team start the investigation.

Objectives: Evaluating the risk of Depression associated with the use of Semaglutide and Tirzepatide, then to suggest regulatory recommendations if required.

Methods: The process of signal review started by extracting the case-reports from the Saudi Pharmacovigilance Center (NPC) database, and global cases from World Health Organization (WHO) database (VigiBase). The extracted local and global cases gone through case by case causality assessment. The second part is screening the literature, in order to retrieve all related publications have described depression in relation to those medications. The last part is the data mining or in other words disproportionality analysis, a statistical methodology used to measure the observed and the expected reporting rate for drug/adverse drug reaction pair. We have used the tool Information Component (IC), it is a tool developed by World Health Organization (WHO) in collaboration with Uppsala Monitoring Center (UMC) to estimate the reporting ratio.

Results: For semaglutide, 520 global cases found in vigibase, while 5 local cases found in SFDA database. For Tirzepatide, 153 global cases while also 5 local cases found. In literature, we found two published case-reports of depression following the use of Semaglutide. We found also a study analyzing psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide, which showed depression as the most commonly reported adverse event (n = 187; 50.3%). The study used EudraVigilance database. Lastly, the disproportionality analysis did not showed any supportive values.

Conclusions: The weighted cumulative evidence identified from the causality assessment of the reported cases, and literature are sufficient to support a causal association between Semaglutide,Tirzepatide and the risk of depression. The SFDA released safety communication recommends health regulators and health care professionals must be aware of this potential risk and it is advisable to monitor any signs or symptoms in treated patients.