Antipsychotic Drugs and Dysregulated Glucose Homeostasis
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Résumé
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.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle