Trial reportAmerican journal of physiology. Endocrinology and metabolism2018
Contribution of parasympathetic muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia.
Trial report in American journal of physiology. Endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Antipsychotic Drugs and Dysregulated Glucose Homeostasis: A Systematic Review and Meta-Analysis.JAMA psychiatry · 2025Pooled it
- The effect of antipsychotic treatment on hormonal, inflammatory, and metabolic biomarkers in healthy volunteers: A systematic review and meta-analysis.Pharmacotherapy · 2022Pooled it
- Reduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 Study.Schizophrenia bulletin · 2023Trial
- Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- The effect of olanzapine on diabetes related index in humans: a systematic review and meta-analysis of randomized controlled trials.Diabetology & metabolic syndrome · 2026Review
- Atypical antipsychotic drugs cause abnormal glucose and lipid metabolism independent of weight gain.European archives of psychiatry and clinical neuroscience · 2025Article
- Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling.Biomedicines · 2024Article
- Drug-induced hyperinsulinemic hypoglycemia: An update on pathophysiology and treatment.Reviews in endocrine & metabolic disorders · 2023Review
- Thymoquinone attenuates olanzapine-induced metabolic disorders in rats.Molecular biology reports · 2023Article
- Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.Pharmaceuticals (Basel, Switzerland) · 2021Review
- An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder.Neuropsychiatric disease and treatment · 2021Review
- Carnosic acid prevented olanzapine-induced metabolic disorders through AMPK activation.Molecular biology reports · 2020Article
- Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia.Endocrine reviews · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet- and activity-controlled inpatient conditions. Before and after 7 days of study drug administration, subjects underwent frequently sampled intravenous glucose tolerance tests with either saline or atropine infused on subsequent days to assess insulin secretion and hepatic insulin extraction in the absence or presence of muscarinic blockade. We found that olanzapine led to an increase in the acute insulin response to glucose, which was not seen with placebo, and was attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data confirmed an increase in insulin secretion with olanzapine, which was blocked by atropine, with a modest reduction in hepatic insulin extraction with olanzapine. These results support the contribution of muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the compensatory hyperinsulinemia that normally serves to prevent deterioration of glucose tolerance under conditions of metabolic challenge.
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Registered trials
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.