Trial reportJAMA psychiatry2025
Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.
Trial report in JAMA psychiatry, 2025. The graph read 6 numbers from its abstract, feeding 4 cells of the map: it supports the treatment in 3, finds no clear difference in 1. It reports registered trial NCT05193578. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
Semaglutide reduced HbA1c by 0.46% of total hemoglobin (95% CI, -0.56% to -0.36%) and body weight by 9.21 kg (95% CI, -11.68 to -6.75).
An HbA1c less than 5.7% of total hemoglobin was achieved in 81% vs 19% of patients treated with semaglutide and placebo, respectively (P < .001); improvements in high-density cholesterol by 10.81 mg/dL (95% CI, 2.70-18.53; P = .007) and triglycerides by -29.20 mg/dL (95% CI, -55.75 to 2.65; P = .03) (to convert to millimoles per liter, multiply by 0.0113) were also observed.
Finally, semaglutide improved physical QoL by 3.75 points on the SF-36v2 (95% CI, 1.52-5.98; P = .001) but had no significant effect on mental QoL scores or PANSS-6 score.
Finally, semaglutide improved physical QoL by 3.75 points on the SF-36v2 (95% CI, 1.52-5.98; P = .001) but had no significant effect on mental QoL scores or PANSS-6 score.
Semaglutide reduced HbA1c by 0.46% of total hemoglobin (95% CI, -0.56% to -0.36%) and body weight by 9.21 kg (95% CI, -11.68 to -6.75).
An HbA1c less than 5.7% of total hemoglobin was achieved in 81% vs 19% of patients treated with semaglutide and placebo, respectively (P < .001); improvements in high-density cholesterol by 10.81 mg/dL (95% CI, 2.70-18.53; P = .007) and triglycerides by -29.20 mg/dL (95% CI, -55.75 to 2.65; P = .03) (to convert to millimoles per liter, multiply by 0.0113) were also observed.
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
GLP-1 receptor agonists×lipids
InconclusiveOpen on the map →What to test next →9 readable studies in this cell: 3 favour the treatment, 6 find no difference, 0 favour the comparator.
GLP-1 receptor agonists×quality of life & behaviour
SupportsOpen on the map →What to test next →14 readable studies in this cell: 4 favour the treatment, 6 find no difference, 4 favour the comparator.
GLP-1 receptor agonists×glycemic control
SupportsOpen on the map →What to test next →40 readable studies in this cell: 97 favour the treatment, 16 find no difference, 10 favour the comparator.
GLP-1 receptor agonists×body weight & composition
SupportsOpen on the map →What to test next →40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes
Open the trial in the graphWho cites it
13 citing papers in PubMed.
- Trial
- Effects of Empagliflozin and Lifestyle Intervention on Improving Body Weight and Other Metabolic Parameters in Atypical Antipsychotics-treated Patients with Schizophrenia Spectrum Disorders-A Double-blind Randomized Placebo-controlled Trial.Schizophrenia bulletin · 2026Trial
- Effectiveness of a Psychiatrist-Led Clinic for Metabolic Health in Severe Mental Illness: A Retrospective Chart Review Study.Acta psychiatrica Scandinavica · 2026Article
- Neuroglia Alterations in the Olfactory Bulbs in Patients with Schizophrenia: An Exploratory Postmortem Study.Life (Basel, Switzerland) · 2026Article
- From brain bioenergetics to hypothalamic glucoregulation: A shared-systems hypothesis for intrinsic dysglycemia in schizophrenia.Reviews in endocrine & metabolic disorders · 2026Review
- Review
- The safety and efficacy of semaglutide in people with schizophrenia spectrum disorders: systematic review and meta-analysis of randomised controlled trials.BJPsych open · 2026Review
- The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients.Schizophrenia bulletin · 2026Article
- Cardiac autonomic neuropathy in patients with SGA-treated schizophrenia: a randomized controlled trial of 30 weeks' treatment with semaglutide.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Clinical practice guidelines for management of schizophrenia in India: A comprehensive overview.Indian journal of psychiatry · 2026Article
- Suicidality as a potential risk and therapeutic target during widespread GLP-1 receptor agonists use: implications of inflammation.Frontiers in synaptic neuroscience · 2026Article
- Comparative efficacy and safety of liraglutide versus metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric patients.Therapeutic advances in psychopharmacology · 2026 · on this mapArticle
- Efficacy and Safety of Semaglutide for Managing Antipsychotic-associated Weight Gain: A Systematic Review and Meta-analysis.Indian journal of endocrinology and metabolismReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
Importance: Patients with schizophrenia have reduced life expectancy due to cardiovascular disease and obesity-related type 2 diabetes, exacerbated by second-generation antipsychotic (SGA) medication. Existing interventions have shown limited effect. Objectives: To assess the effect of the once-weekly glucagon-like peptide-1 receptor agonist semaglutide in SGA-treated adults (aged 18-60 years) with schizophrenia, prediabetes (glycosylated hemoglobin A1c [HbA1c], 5.7%-6.4% of total hemoglobin) (to convert HbA1c from percentage of total hemoglobin to mmol/mol, use the following formula: (HbA1c % - 2.152)/0.09148), and overweight or obesity (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, ≥27). Design, Setting, and Participants: This placebo-controlled, double-blinded randomized clinical trial was conducted from January 2022 to May 2024, with 30 weeks of follow-up, among regional community-based mental health services in 2 regions of Denmark (Region of Southern Denmark and Region of Zealand). SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo. Data analysis was completed from May 2024 to January 2025. Intervention: Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks. Main Outcomes and Measures: The primary outcome was change in HbA1c. Secondary end points included changes in body weight, schizophrenia symptoms based on Positive and Negative Syndrome Scale 6 (PANSS-6) score, and physical and mental quality of life (QoL) (assessed via the 36-item Short Form Survey, version 2 [SF-36v2]). Results: A total of 154 patients were recruited and randomized 1:1 to semaglutide or placebo (87 female participants (56.5%); mean [SD] age, 38.3 [10.7] years). Of 154 randomized patients, 141 (91.5%) completed the trial-74 of 77 patients randomized to semaglutide (96%) and 67 of 77 randomized to placebo (87%). Semaglutide reduced HbA1c by 0.46% of total hemoglobin (95% CI, -0.56% to -0.36%) and body weight by 9.21 kg (95% CI, -11.68 to -6.75). An HbA1c less than 5.7% of total hemoglobin was achieved in 81% vs 19% of patients treated with semaglutide and placebo, respectively (P < .001); improvements in high-density cholesterol by 10.81 mg/dL (95% CI, 2.70-18.53; P = .007) and triglycerides by -29.20 mg/dL (95% CI, -55.75 to 2.65; P = .03) (to convert to millimoles per liter, multiply by 0.0113) were also observed. Finally, semaglutide improved physical QoL by 3.75 points on the SF-36v2 (95% CI, 1.52-5.98; P = .001) but had no significant effect on mental QoL scores or PANSS-6 score. Gastrointestinal symptoms were more frequent in semaglutide-treated patients. A few semaglutide-treated patients were hospitalized more frequently than observed in the placebo-treated group, but the number of serious adverse effects did not differ between groups. Conclusions and Relevance: In this multicenter, double-blinded randomized clinical trial, 30 weeks of administration of semaglutide, up to 1.0 mg/week, was safe, lowered blood glucose (as measured by HbA1c) and weight, and improved physical QoL in SGA-treated patients with schizophrenia, prediabetes, and obesity without worsening mental health. Trial Registration: ClinicalTrials.gov Identifier: NCT05193578.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.