Ozempic and Suicidal Thoughts: Insights from a Study

New data revealed a link between Ozempic and Suicidal thoughts [Ref]. The study compared Semaglutide with Liraglutide. It also compared Dapagliflozin, Orlistat, and metformin as active comparator drugs.

The data suggests a potential link between semaglutide and liraglutide use and suicidal or self-injurious behavior, particularly for semaglutide.

Although these cases are rare, the findings underscore the importance of carefully monitoring these patients.

Obesity Epidemic and GLP-1 Medications:

In the past ten years, obesity has become a significant health crisis. During this time, medications that target the glucagon-like peptide-1 (GLP-1) receptor have changed how we treat obesity.

Originally developed for managing type 2 diabetes, these drugs not only help regulate blood sugar but also reduce appetite, slow down stomach emptying, and decrease the release of the hormone glucagon.

The weight loss effects of GLP-1 receptor agonists (RAs) like liraglutide and semaglutide have become widely known, even leading to shortages due to their popularity beyond diabetes treatment.

Popularity and Demand:

With about 10% of type 2 diabetes patients in the U.S. now prescribed GLP-1 RAs, there has been concern about ensuring enough supply for those who need them most.

Regulatory authorities worldwide have advised healthcare professionals to prioritize these medications for patients with diabetes, rather than for off-label uses.

Safety Concerns and Ongoing Investigations:

Despite their benefits, there are serious safety concerns about GLP-1 RAs. Recently, reports of suicidal thoughts or self-harm linked to liraglutide and semaglutide have prompted investigations by major health agencies, including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

Earlier trials showed some instances of suicidal thoughts with liraglutide, but no such cases were reported with semaglutide.

However, it’s important to note that people with a history of suicidal thoughts were generally excluded from these studies, so the real-world risk may be different.

Global Impact and Investigations:

With over 20 million people using these medications each year, the EMA’s investigation could have a significant global impact. Both the EMA and FDA have stated that, so far, they haven’t found clear evidence linking GLP-1 RAs to suicide.

However, investigations are ongoing, and warnings about potential mental health risks are required for medications that affect the brain and are used for long-term weight management.

What’s Next?

The investigation by the EMA, which started in July 2023, was expected to conclude by November 2023 but was extended into 2024.

During this time, both the UK and US health agencies have also started their reviews. The final outcomes of these investigations will determine whether additional warnings or restrictions will be placed on these widely used medications.

Summary of Suicidal and Self-Injurious Adverse Drug Reactions (ADRs) Associated with Semaglutide and Liraglutide

Overview of Reported Cases

As of August 30, 2023, data from a comprehensive database containing over 36 million reports identified 107 cases of suicidal and/or self-injurious adverse drug reactions (ADRs) associated with semaglutide and 162 cases associated with liraglutide.

These cases account for 0.35% of all semaglutide reports and 0.31% of all liraglutide reports.

• Semaglutide:

  • Median age of patients: 48 years; 55% were female. Median treatment duration before ADRs: 24 days.

• Liraglutide:

  • Median age of patients: 47 years; 61% were female. Median treatment duration before ADRs: 46 days.

Reasons for Prescription

• Off-label use:

  • 31.8% (semaglutide) and 33.9% (liraglutide)

• Weight management:

  • 26.2% (semaglutide) and 24.7% (liraglutide)

• Diabetes treatment:

  • 24.3% (semaglutide) and 20.4% (liraglutide)

• Polycystic ovary syndrome (PCOS):

  • 0.9% for both drugs

Outcomes and Comedications

• Resolution of Suicidal Ideation:

  • Suicidal thoughts resolved in 62.5% of the cases after stopping the drug.

• Common Comedications:

  • Semaglutide: Antidiabetics (15.9%) and antidepressants (13.1%)
  • Liraglutide: Antidiabetics (30.3%) and antidepressants (18.5%)

Suicidal and Self-Injurious ADRs

• Semaglutide:

  • Suicidal ideation: 88%
  • Intentional overdose: 6.5%
  • Suicide attempt: 6.5%
  • Fatal outcomes: 6.5%

• Liraglutide:

  • Suicidal ideation: 71.6%
  • Completed suicide: 11.7%
  • Suicide attempt: 9.9%
  • Fatal outcomes: 14.8%

Disproportionality Analysis

• Semaglutide-associated suicidal ideation:
  • Significantly higher than all medications, with a risk odds ratio (ROR) of 1.45. The risk remained high even with comedications like antidepressants and benzodiazepines.
• Comparative Analysis:
  • Semaglutide showed a higher risk of suicidal ideation compared to dapagliflozin, metformin, and orlistat.

Gender Differences

• Men:
  • Higher risk of Semaglutide-associated suicidal ideation (ROR: 1.51).
• Women:
  • A similar trend was observed, but the confidence interval suggested less certainty.

Trends Over Time

From the market introduction until August 2023, reports of suicidal ADRs slightly increased for both drugs:

• Semaglutide: From 0% in 2017 to 0.8% in 2023.
• Liraglutide: From 0.09% in 2014 to 0.4% in 2023.

Conclusion

The data suggests a potential link between semaglutide and liraglutide use and suicidal or self-injurious behavior, particularly for semaglutide.

Although these cases are rare, the findings underscore the importance of careful monitoring, especially when these drugs are used off-label or in combination with other psychiatric medications. Further investigations and close clinical supervision are warranted.