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Antipsychotic Drugs and Dysregulated Glucose Homeostasis

2025· article· en· W4413758293 on OpenAlex
Emily C. C. Smith, Sri Mahavir Agarwal, Kristoffer Panganiban, Kateryna Maksyutynska, Jonathan Monteiro, Jiwon Lee, Femin Prasad, Andrew Ji, Divia Shah, Samantha Cavalier, Reva U. Prabhune, Emril Radoncic, Zilu Yang, Kaitlin Fuller, Michael J. McCarthy, Tyler R. Prestwood, Jacob S. Ballon, Christoph U. Correll, Margaret Hahn, Zachary Freyberg

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJAMA Psychiatry · 2025
Typearticle
Languageen
FieldMedicine
TopicSchizophrenia research and treatment
Canadian institutionsSt. Francis Xavier UniversityDiabetes CanadaUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Institute of Diabetes and Digestive and Kidney Diseases
KeywordsGlucose homeostasisAntipsychoticMedicinePharmacologyHomeostasisAntipsychotic drugNeuroscienceDiabetes mellitusSchizophrenia (object-oriented programming)PsychologyInternal medicinePsychiatryEndocrinologyInsulin resistance

Abstract

fetched live from OpenAlex

Importance: Antipsychotic drug (AP)-induced glucose homeostasis changes are often attributed to AP-induced weight gain. Nevertheless, dysregulated glucose control can occur independently of weight gain. Objective: To examine the association between AP use and glucose homeostasis while considering weight gain propensity, medication type, and treatment duration. Data Sources: MEDLINE, Embase, PsychINFO, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through February 3, 2025. Study Selection: Blinded randomized clinical trials (RCTs) comparing changes in glucose homeostasis-related parameters between patients with severe mental illness or healthy volunteers assigned to AP or control (placebo or no intervention) groups were included. Studies were limited to English-language human studies without restrictions on study length, AP type, or previous AP exposure. Of 22 773 unique citations, 163 RCTs met inclusion criteria, with 127 studies included in the meta-analysis. Data Extraction and Synthesis: Each article was screened independently by 2 authors using predefined inclusion and exclusion criteria. Data extraction and risk of bias assessment were completed using a standardized spreadsheet. Data were analyzed via random-effects meta-analysis, with subgroup analyses for diagnosis, study length, AP type, age, concomitant medication use, and previous AP exposure. Metaregressions identified covariate effects. Data analysis was completed from October 2023 to February 2025. Main Outcomes and Measures: Primary study outcomes were changes in fasting glucose, fasting insulin, and glycated hemoglobin (HbA1c) following AP treatment. Secondary outcomes included any other glucose metabolism-related parameters including, but not limited to, insulin resistance and hyperglycemia. Results: A total of 35 952 AP-treated patients and 19 010 placebo-treated patients were included in the qualitative synthesis, while 28 975 AP-treated and 15 101 placebo-treated patients were included in the meta-analysis. AP use was associated with significantly increased fasting glucose (mean difference [MD], 0.72 mg/dL; 95% CI, 0.54-1.08 [to convert to millimoles per liter, multiply by 0.0555]; P < .001), fasting insulin (MD, 1.94 μIU/mL; 95% CI, 1.28-2.61 [to convert to picomoles per liter, multiply by 6]; P < .001), glycated hemoglobin (MD, 0.04%; 95% CI, 0.02%-0.05% [to convert to proportion of total hemoglobin, multiply by 0.01]; P < .001), and hyperglycemia (odds ratio, 1.29; 95% CI, 1.04-1.59; P = .02) vs placebo. Findings were corroborated in healthy volunteers. Subgroup analyses suggested that AP type, diagnosis, age, concomitant medication use, and previous AP exposure do not consistently affect dysglycemia risk. In metaregression analyses, AP-associated dysregulations in glucose homeostasis were independent of study length and AP dose. Conclusions and Relevance: In this systematic review and meta-analysis, results indicate that AP exposure significantly disrupts glucose homeostasis independent of exposure time, dose, diagnosis, and weight gain propensity. Increased awareness of AP-induced dysregulations in glucose homeostasis alongside ongoing metabolic monitoring and potential treatment is warranted.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.712
Threshold uncertainty score0.528

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.287
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it