The latest enhance in GLP-1 (glucagon-like peptide-1) receptor agonist use not just for diabetes but additionally for weight reduction has dominated headlines over the previous few years. Nevertheless, how these medicine have an effect on one’s psychological well-being is much less effectively understood. There have been issues concerning the influence GLP-1 receptor agonists have on suicidal ideas. Some have additionally touted the potential advantages to psychological well being these medicine pose, together with decreased substance use and enhancements in temper. Higher clarifying how GLP-1s affect psychological well being, notably amongst these with pre-existing psychiatric sickness, is vital for informing remedy selections and understanding who one of the best candidates for such drugs could also be.
To start to deal with this hole within the literature, Taipale and colleagues (2026) used the nationwide Swedish well being registers to match using GLP-1 receptor agonists with non-use and with use of different second-line antidiabetic drugs amongst people with a pre-existing analysis of despair or anxiousness. They have been particularly all in favour of understanding whether or not using this medicine is related to worsening psychological well being, in addition to worsening of substance use dysfunction and self-harm. The authors used a within-individual design, evaluating these interventions inside the similar particular person (i.e., how an individual taking a GLP-1 compares with when that very same particular person isn’t taking a GLP-1).
Strategies
The authors used Swedish nationwide well being registers to collect knowledge from 95,490 individuals with a premorbid analysis of despair or anxiousness who have been prescribed non-insulin antidiabetic medicine between 2009 and 2022, which have been analysed on this examine utilizing a within-individual design.
The authors in contrast every particular person’s danger of worsening psychological well being (outlined as a mixture of psychiatric hospitalisations, sick go away from work exceeding 14 days for psychiatric causes, hospitalisation as a consequence of self-harm, or demise by suicide) in periods of GLP-1 use in opposition to their danger once they weren’t utilizing the medicine. Secondary analyses additionally in contrast various kinds of antidiabetic drugs with each other inside the similar people. The within-individual design the authors used eliminates the consequences of traits that don’t change over time (e.g., persona, different comorbidities).
Outcomes
Among the many 95,490 individuals included on this examine, the bulk have been feminine (59.7%) and had a analysis of tension (81.5%), although greater than half had a analysis of despair (54.9%) and a few third (36.4%) had each situations. A few quarter (23.5%) of the overall cohort have been prescribed GLP-1 receptor agonists, of whom 59.8% have been prescribed semaglutide and 46.9% liraglutide (some individuals used a couple of GLP-1 throughout follow-up).
| Final result | Semaglutide | Liraglutide | Dulaglutide | Exenatide | Any GLP-1 receptor agonist |
|---|---|---|---|---|---|
| Worsening psychological sickness (essential consequence) | 0.58 (0.51 to 0.65) | 0.82 (0.76 to 0.89) | 1.01 (0.85 to 1.20) | 1.01 (0.69 to 1.46) | 0.76 (0.71 to 0.82) |
| Psychiatric or self-harm hospitalisation | 0.72 (0.59 to 0.89) | 0.89 (0.76 to 1.05) | 1.09 (0.83 to 1.44) | 1.28 (0.61 to 2.68) | Not reported |
| Sick go away over 14 days for psychiatric causes | 0.55 (0.47 to 0.64) | 0.88 (0.80 to 0.97) | 0.92 (0.73 to 1.16) | 1.14 (0.73 to 1.76) | Not reported |
| Worsening despair | 0.56 (0.44 to 0.71) | 0.74 (0.64 to 0.87) | 0.71 (0.51 to 1.01) | 1.40 (0.74 to 2.62) | 0.70 (0.62 to 0.79) |
| Worsening anxiousness | 0.62 (0.52 to 0.73) | 0.91 (0.81 to 1.02) | 1.11 (0.86 to 1.44) | 1.20 (0.73 to 1.99) | 0.84 (0.76 to 0.92) |
| Worsening substance use dysfunction | 0.53 (0.35 to 0.80) | 1.05 (0.80 to 1.38) | 1.01 (0.60 to 1.72) | Too few occasions | 0.84 (0.68 to 1.04) |
| Hospital-treated self-harm | 0.51 (0.20 to 1.28) | 0.54 (0.28 to 1.07) | 0.39 (0.14 to 1.09) | Too few occasions | 0.56 (0.34 to 0.92) |
Use of each semaglutide and liraglutide was related to decreased worsening of psychological well being issues in contrast with intervals when the identical people didn’t use GLP-1s. When semaglutide was in contrast with different GLP-1 Receptor agonists, semaglutide was related to a considerably decreased danger of worsening psychological well being issues. Men and women didn’t considerably differ of their decreased danger of worsening psychological well being issues throughout all GLP-1 receptor agonists besides liraglutide, for which there was solely a decreased danger of worsening psychological well being issues in ladies, however not in males.
Relating to particular elements of worsening psychological well being issues, semaglutide was related to a decreased danger of worsening despair, worsening anxiousness, and worsening substance use, however liraglutide was solely related to a decreased danger of worsening despair. Any use of GLP-1 receptor agonists was related to decreased danger of self-harm. Amongst inpatient occasions, semaglutide was related to a decreased danger of psychiatric or self-harm hospitalisation. Each semaglutide and liraglutide have been additionally related to a decrease danger of sick go away as a consequence of any psychiatric purpose. When put next with different second-line antidiabetics, semaglutide was once more related to a decrease danger of worsening psychological well being issues, whereas dapagliflozin and sitagliptin have been linked to a larger danger of worsening psychological well being issues in contrast with empagliflozin.
| Remedy | Adjusted hazard ratio (95% confidence interval) | In contrast with empagliflozin |
|---|---|---|
| Semaglutide | 0.73 (0.62 to 0.87) | Decrease danger |
| Liraglutide | 1.14 (1.00 to 1.30) | No clear distinction |
| Dapagliflozin | 1.24 (1.02 to 1.52) | Increased danger |
| Sitagliptin | 1.49 (1.31 to 1.68) | Increased danger |
Conclusions
The authors concluded that, amongst individuals with established despair or anxiousness who have been additionally being handled with an antidiabetic, semaglutide and (to a lesser extent) liraglutide have been related to considerably decrease danger of worsening psychological well being issues in contrast with intervals of time once they weren’t utilizing these drugs, whereas exenatide and dulaglutide weren’t.
They counsel that these findings point out differing GLP-1s might have completely different advantages, although they word that GLP-1 receptor agonists as a bunch have been related to a decrease danger of self-harm (the examine lacked the facility to check particular person medicine). The authors name for a future randomised managed trial of GLP-1 receptor agonist use in individuals with diabetes and despair, anxiousness, or each psychiatric situations to enhance understanding of the precise advantages GLP-1 receptor agonists might have in these populations.
Strengths and limitations
Using a within-individual design is by far the best energy of this examine. By having every particular person act as their very own comparator, the examine removes the impact of steady variations between individuals who take GLP-1s and those that don’t (akin to persona or baseline sickness severity). It may’t rule out elements that change over time, akin to why somebody begins or stops the drug, and the authors acknowledge doable residual confounding. Furthermore, the very giant pattern measurement provides the examine the facility to detect modest associations.
One limitation of this examine is the absence of scientific severity measures. The authors have been unable to look at to what extent the decreased danger of worsening psychological well being issues seen throughout medicine use intervals is a mirrored image of modifications in weight or symptom severity that may be anticipated throughout medicine use. Moreover, there have been considerably smaller samples in analyses of dulaglutide and exenatide. Subsequently, the null findings for these medicine could also be a problem of energy reasonably than an absence of impact.
One other limitation of this examine is that there have been various indications for using GLP-1 receptor agonists among the many examine cohort, and it’s unclear whether or not the indication (for instance, somebody taking the medicine for diabetes vs. for weight reduction) was related to variations in danger of worsening psychological well being issues. Equally, for the reason that majority of individuals included on this examine have been prescribed these drugs for diabetes, replicating this examine with a pattern of individuals solely taking GLP-1 receptor agonists for weight reduction is vital to generalise the findings to an ever-increasing group of people now prescribed GLP-1 receptor agonists for this indication.
Implications for apply
This examine is a vital first step in understanding how GLP-1 receptor agonists might have an effect on psychological well being amongst people with diabetes or weight problems and comorbid despair or anxiousness. The findings counsel that maybe GLP-1 use might assist with psychological well being alongside bodily well being. Nevertheless, a randomised managed trial is required to higher perceive these preliminary findings.
For prescribers, these outcomes additionally counsel that every GLP-1 receptor agonist might have completely different results on psychological well being. The findings additionally counsel that semaglutide could also be a smart possibility for individuals with diabetes and a pre-existing analysis of despair or anxiousness; the case for liraglutide is weaker, because it did no higher than empagliflozin within the head-to-head comparability. Nevertheless, on condition that these findings haven’t but been replicated in a randomised managed trial and due to particular person variations, it is very important assess and monitor modifications in every particular person’s psychological well being signs all through remedy and alter accordingly.
Assertion of pursuits
Alexandra Allam has no conflicts of curiosity to declare, however acknowledges AI (Claude, Anthropic) use to assist with the modifying of the weblog textual content.
Editor
Edited by Dr Dafni Katsampa.
Hyperlinks
Main paper
Heidi Taipale, Mark Taylor, Markku Lähteenvuo, Ellenor Mittendorfer-Rutz, Antti Tanskanen, Jari Tiihonen. (2026) Affiliation between GLP-1 receptor agonist use and worsening psychological sickness in individuals with despair and anxiousness in Sweden: a nationwide cohort examine. Lancet Psychiatry 2026; 13: 327–35.
