GLP-1 Receptor Agonists Show Potential to Reduce Mental Health Risks in People with Diabetes and Obesity

Key Takeaways: 

• GLP-1 receptor agonists were associated with a reduced risk of worsening mental illness in people living with diabetes and co-existing anxiety or depression
  
• Semaglutide and liraglutide showed the most notable effects, including reductions in depression, anxiety, and self-harm risk
  
• Findings from a large Swedish cohort study highlight potential dual benefits, though randomised trials are still needed
  
  
  

Growing interest in the mental health effects of GLP-1 therapies

A large national cohort study from Sweden, published in The Lancet Psychiatry, suggests that glucagon-like peptide-1 receptor agonists may offer benefits beyond metabolic control. The findings indicate that medications such as semaglutide and liraglutide could help reduce the risk of worsening mental illness in people living with diabetes and co-existing obesity, anxiety, or depression.

GLP-1 receptor agonists are widely used in the management of type 2 diabetes and obesity. However, their impact on mental health outcomes has remained uncertain, with previous research producing mixed results. This study contributes new large-scale evidence suggesting a potentially protective effect.

Mental illness and diabetes – a high-risk overlap

People living with diabetes are known to have a higher risk of mental health conditions, including depression, anxiety, and suicide. This overlap creates a complex clinical picture, where both metabolic and psychological factors influence outcomes.

The researchers emphasised that understanding how commonly prescribed antidiabetic medications affect mental health is essential, particularly in populations already at elevated psychiatric risk.

Study design and population

The study analysed data from Swedish national electronic health registers, covering the period from 2009 to 2022. Researchers identified individuals with diagnosed depression or anxiety who were also receiving antidiabetic treatment.

Participants who used GLP-1 receptor agonists were compared with those who did not use these medications, as well as with individuals taking other second-line antidiabetic therapies.

In total, nearly 95,500 people were included in the analysis. Approximately 60% of participants were female and 40% male, with a mean age of around 50 years. Data on ethnicity were not available.

During the follow-up period, almost 22,500 individuals used GLP-1 receptor agonists.

Outcomes measured

The study assessed several primary and secondary outcomes related to mental health.

Primary outcomes included:

• Psychiatric hospitalisation
• Sick leave exceeding 14 days due to psychiatric reasons
• Hospitalisation due to self-harm
• Death by suicide
  

Secondary outcomes included:

• Worsening symptoms of depression or anxiety
• Substance use disorder
• Self-harm
  

Reduced risk of worsening mental illness

The findings indicated that some GLP-1 receptor agonists were associated with a lower risk of worsening mental health outcomes.

Semaglutide and liraglutide were linked to a 42% and 18% lower risk of worsening mental illness, respectively, compared with people who did not use GLP-1 therapies.

When examining specific outcomes:

• Semaglutide was associated with a 44% lower risk of worsening depression
• A 38% reduced risk of worsening anxiety
• A 47% lower likelihood of worsening substance use disorder

Liraglutide showed a more limited effect, with a 26% reduction in the risk of worsening depression, but no significant impact on other mental health outcomes.

Other GLP-1 receptor agonists, including exenatide and dulaglutide, did not demonstrate meaningful changes in risk.

Impact on self-harm risk

One of the most notable findings was the association between GLP-1 receptor agonist use and a reduced risk of self-harm.

Overall, these medications were linked to a 44% lower risk of self-harm compared with non-use, suggesting a potentially important role in mitigating severe psychiatric outcomes in this population.

Implications for clinical practice

The results suggest that certain GLP-1 receptor agonists may provide dual therapeutic benefits for people living with diabetes and obesity, addressing both metabolic and mental health outcomes.

However, the authors cautioned that observational findings cannot establish causality. They highlighted the need for randomised controlled trials to confirm these associations and better understand the mechanisms involved.

Conclusion

This large Swedish cohort study provides evidence that some GLP-1 receptor agonists, particularly semaglutide and liraglutide, may be associated with reduced risks of worsening mental illness and self-harm in people living with diabetes and co-existing psychiatric conditions.

While further research is required, the findings point towards a potentially valuable role for these medications in addressing the interconnected challenges of metabolic and mental health.

CCH insight:

Yet more positive news about GLP-1 medications. This is very encouraging, particularly as there are so many drugs that have negative side-effects regarding mental health. However, this study only shows an association, and not causation, and did not adjust for the possible effects of losing weight – those on GLP-1 therapy may have experienced improved mood and mental health due to the fact they were losing weight, rather than as a direct effect of the drug. More research is needed to elucidate the complex interactions of obesity and mental health and the effects of GLP-1 medications.