The latest enhance in GLP-1 (glucagon-like peptide-1) receptor agonist use not just for diabetes but in addition 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 impression 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, significantly amongst these with pre-existing psychiatric sickness, is important for informing remedy selections and understanding who the perfect candidates for such drugs could also be.
To start to handle this hole within the literature, Taipale and colleagues (2026) used the nationwide Swedish well being registers to check 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 melancholy or anxiousness. They had been particularly excited about understanding whether or not using this treatment 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 throughout the similar individual (i.e., how an individual taking a GLP-1 compares with when that very same individual will not be taking a GLP-1).
Strategies
The authors used Swedish nationwide well being registers to collect knowledge from 95,490 members with a premorbid analysis of melancholy or anxiousness who had been prescribed non-insulin antidiabetic treatment between 2009 and 2022, which had been analysed on this research utilizing a within-individual design.
The authors in contrast every individual’s threat of worsening psychological well being (outlined as a mixture of psychiatric hospitalisations, sick depart from work exceeding 14 days for psychiatric causes, hospitalisation resulting from self-harm, or loss of life by suicide) in periods of GLP-1 use in opposition to their threat after they weren’t utilizing the treatment. Secondary analyses additionally in contrast various kinds of antidiabetic drugs with each other throughout the similar people. The within-individual design the authors used eliminates the results of traits that don’t change over time (e.g., character, different comorbidities).
Outcomes
Among the many 95,490 members included on this research, the bulk had been feminine (59.7%) and had a analysis of tension (81.5%), although greater than half had a analysis of melancholy (54.9%) and a couple of third (36.4%) had each circumstances. A couple of quarter (23.5%) of the whole cohort had been prescribed GLP-1 receptor agonists, of whom 59.8% had been prescribed semaglutide and 46.9% liraglutide (some individuals used multiple GLP-1 throughout follow-up).
| Consequence | Semaglutide | Liraglutide | Dulaglutide | Exenatide | Any GLP-1 receptor agonist |
|---|---|---|---|---|---|
| Worsening psychological sickness (major final result) | 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 depart 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 melancholy | 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 threat of worsening psychological well being issues. Ladies and men didn’t considerably differ of their decreased threat of worsening psychological well being issues throughout all GLP-1 receptor agonists besides liraglutide, for which there was solely a decreased threat of worsening psychological well being issues in girls, however not in males.
Concerning particular components of worsening psychological well being issues, semaglutide was related to a decreased threat of worsening melancholy, worsening anxiousness, and worsening substance use, however liraglutide was solely related to a decreased threat of worsening melancholy. Any use of GLP-1 receptor agonists was related to decreased threat of self-harm. Amongst inpatient occasions, semaglutide was related to a decreased threat of psychiatric or self-harm hospitalisation. Each semaglutide and liraglutide had been additionally related to a decrease threat of sick depart resulting from any psychiatric motive. In comparison with different second-line antidiabetics, semaglutide was once more related to a decrease threat of worsening psychological well being issues, whereas dapagliflozin and sitagliptin had been linked to a better threat of worsening psychological well being issues in contrast with empagliflozin.
| Medicine | Adjusted hazard ratio (95% confidence interval) | In contrast with empagliflozin |
|---|---|---|
| Semaglutide | 0.73 (0.62 to 0.87) | Decrease threat |
| Liraglutide | 1.14 (1.00 to 1.30) | No clear distinction |
| Dapagliflozin | 1.24 (1.02 to 1.52) | Greater threat |
| Sitagliptin | 1.49 (1.31 to 1.68) | Greater threat |
Conclusions
The authors concluded that, amongst individuals with established melancholy or anxiousness who had been additionally being handled with an antidiabetic, semaglutide and (to a lesser extent) liraglutide had been related to considerably decrease threat of worsening psychological well being issues in contrast with intervals of time after they weren’t utilizing these drugs, whereas exenatide and dulaglutide weren’t.
They counsel that these findings point out differing GLP-1s could have totally different advantages, although they observe that GLP-1 receptor agonists as a bunch had been related to a decrease threat of self-harm (the research lacked the ability 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 melancholy, anxiousness, or each psychiatric circumstances to enhance understanding of the precise advantages GLP-1 receptor agonists could have in these populations.
Strengths and limitations
Using a within-individual design is by far the best power of this research. By having every individual act as their very own comparator, the research removes the impact of secure variations between individuals who take GLP-1s and people who don’t (corresponding to character or baseline sickness severity). It may’t rule out components that change over time, corresponding to why somebody begins or stops the drug, and the authors acknowledge doable residual confounding. Furthermore, the very massive pattern measurement offers the research the ability to detect modest associations.
One limitation of this research is the absence of scientific severity measures. The authors had been unable to look at to what extent the decreased threat of worsening psychological well being issues seen throughout treatment use intervals is a mirrored image of modifications in weight or symptom severity that may be anticipated throughout treatment use. Moreover, there have been considerably smaller samples in analyses of dulaglutide and exenatide. Due to this fact, the null findings for these medicine could also be a difficulty of energy moderately than an absence of impact.
One other limitation of this research is that there have been various indications for using GLP-1 receptor agonists among the many research cohort, and it’s unclear whether or not the indication (for instance, somebody taking the treatment for diabetes vs. for weight reduction) was related to variations in threat of worsening psychological well being issues. Equally, for the reason that majority of members included on this research had been prescribed these drugs for diabetes, replicating this research with a pattern of members solely taking GLP-1 receptor agonists for weight reduction is important to generalise the findings to an ever-increasing group of people now prescribed GLP-1 receptor agonists for this indication.
Implications for apply
This research is a obligatory first step in understanding how GLP-1 receptor agonists could have an effect on psychological well being amongst people with diabetes or weight problems and comorbid melancholy or anxiousness. The findings counsel that maybe GLP-1 use could assist with psychological well being alongside bodily well being. Nevertheless, a randomised managed trial is required to raised perceive these preliminary findings.
For prescribers, these outcomes additionally counsel that every GLP-1 receptor agonist could have totally different results on psychological well being. The findings additionally counsel that semaglutide could also be a wise possibility for individuals with diabetes and a pre-existing analysis of melancholy or anxiousness; the case for liraglutide is weaker, because it did no higher than empagliflozin within the head-to-head comparability. Nevertheless, provided that these findings haven’t but been replicated in a randomised managed trial and due to particular person variations, you will need to assess and monitor modifications in every particular person’s psychological well being signs all through remedy and regulate accordingly.
Assertion of pursuits
Alexandra Allam has no conflicts of curiosity to declare, however acknowledges AI (Claude, Anthropic) use to assist with the enhancing 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 melancholy and anxiousness in Sweden: a nationwide cohort research. Lancet Psychiatry 2026; 13: 327–35.
