FDA Investigates the Safety of GLP-1 Weight Loss Drugs

Yesterday, on January 11, 2024, the United States FDA issued a drug safety communication updating the public on an ongoing investigation of glucagon-like peptide-1 receptor agonists. The administration evaluated the link between using these medications and suicidal thoughts, noting that there is no causal relationship.

Glucagon-like peptide-1`receptor agonists (GLP-1 Ras), commonly called GLP-1 drugs, have become an increasingly popular class of medications. Their duality in treating type 2 diabetes and managing weight in overweight and obese patients has drawn attention to this relatively new class of drugs.

To date, the FDA has approved 13 brand-name GLP-1 drugs with multiple active ingredients, including exenatide, liraglutide, liraglutide with insulin degludec, liraglutide with insulin glargine, dulaglutide, lixisenatide, semaglutide and tirzepatide.

Among the 13 brand-name compounds, only 3 have been indicated to manage obesity. However, many of the compounds that have only been formally approved to manage type 2 diabetes — most notably, Ozempic — have been used to manage weight in obese and overweight patients.

Despite the proven efficacy of these weight management medications, patients taking these drugs may experience a broad range of side effects.

One side effect that particularly concerned patients, providers, and scientists was the risk of suicidal thoughts. Prompted by reports of suicidal thoughts or actions from patients taking this class of medication, the FDA evaluated the relationship between the two.

Based on the investigation, the FDA concluded, “Because the information provided was often limited and because these events can be influenced by other potential factors, we determined that the information in these reports did not demonstrate a clear relationship with the use of GLP-1 RAs. Similarly, our reviews of the clinical trials, including large outcome studies and observational studies, did not find an association between the use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

In fact, a recent study published in Nature Medicine revealed that the use of GLP-1 drugs may actually lower the risk of suicidal ideation compared to using non-GLP-1 anti-obesity drugs.

According to the study, the risk of incident suicidal ideation was roughly 73% lower in those taking GLP-1 drugs. Similarly, the risk of recurrent suicidal ideation was approximately 56% lower in those taking GLP-1 drugs.

Although additional studies are necessary to understand the correlation between the two, the FDA’s preliminary report maintains that GLP-1 drugs do not impact the risk of suicidal thoughts.