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TAAR1 agonist ulotaront delays gastric emptying of solids in patients with schizophrenia and concurrent metabolic syndrome with prediabetes.

Authors :
Milanović, Snežana
Dedic, Nina
Lew, Robert
Burton, Duane
Koblan, Kenneth S.
Camilleri, Michael
Hopkins, Seth C.
Source :
Diabetes, Obesity & Metabolism. Jun2024, Vol. 26 Issue 6, p2466-2475. 10p.
Publication Year :
2024

Abstract

Background: Metabolic syndrome (MetS), which can be induced or exacerbated by the current class of antipsychotic drugs, is highly prevalent in patients with schizophrenia and presents significant challenges to lifetime disease management. Supported by initial clinical results, trace amine‐associated receptor 1 (TAAR1) agonists have emerged as potential novel treatments for schizophrenia. Notably, non‐clinical studies have also shown weight‐lowering and glucoregulatory effects of TAAR1 agonists, including the investigational agent ulotaront. However, the translatability of these findings to humans has not been adequately assessed. Given that delayed gastric emptying (GE) was identified as a potential mechanism contributing to the metabolic benefits of TAAR1 agonists in rodents, the aim of this study was to evaluate the effect of ulotaront on GE in patients with schizophrenia and concurrent MetS with prediabetes. Methods: Patients with schizophrenia were randomized to receive a single oral dose of ulotaront (150 mg) and their previous antipsychotic (PA) in an open‐label, crossover, two‐sequence design (NCT05402111). Eligible participants fulfilled at least three of five MetS criteria and had prediabetes defined by elevated glycated haemoglobin (5.7‐6.4%) and/or fasting homeostatic model assessment of insulin resistance (i.e. ≥2.22). Following an overnight fast and 4 h post‐dose, participants ingested a 99mTc‐sulphur colloid radiolabelled egg meal (320 kcal, 30% fat). GE was measured by scintigraphy over 4 h. Endpoints included GE of solids half‐time (T1/2) and percentage gastric retention at 1, 2 and 4 h. Results: Thirty‐one adults were randomized and 27 completed the study. Ulotaront significantly delayed GE of solids [median GE T1/2 ulotaront at 139 min (119, 182) vs. the participant's PA of 124 min (109, 132), p =.006]. A significant increase in gastric retention was seen in the ulotaront versus the PA group at 1 h (80% vs. 75%, p =.015), 2 h (61% vs. 50%, p =.023) and 4 h (17% vs. 7%, p =.002) post‐meal. Conclusion: Ulotaront delayed the GE of solids in patients with schizophrenia and concurrent MetS with prediabetes. Additional studies are needed to assess whether treatment with TAAR1 agonists is associated with weight loss and glucoregulatory improvement. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14628902
Volume :
26
Issue :
6
Database :
Academic Search Index
Journal :
Diabetes, Obesity & Metabolism
Publication Type :
Academic Journal
Accession number :
177114127
Full Text :
https://doi.org/10.1111/dom.15569