Arginine vasopressin dynamics in relation to food intake and 8-week intranasal oxytocin treatment in adults with obesity

J Clin Endocrinol Metab. 2025 May 2:dgaf237. doi: 10.1210/clinem/dgaf237. Online ahead of print.

ABSTRACT

CONTEXT: Oxytocin (OXT) and arginine-vasopressin (AVP) are structurally similar hypothalamic-pituitary peptides with broad physiologic actions including regulation of caloric intake and metabolism. While OXT is under investigation as an anti-obesity therapeutic, there are no data on endogenous AVP levels in relation to eating behavior in humans. Further, the effects of exogenous OXT on AVP dynamics, which could impact safety of treatment given AVP effects on water balance, are not well understood.

OBJECTIVE: To define secretory dynamics of circulating AVP around a standardized meal and in response to 8-weeks intranasal (IN) OXT vs. placebo in adults with obesity.

DESIGN: Cross-sectional and longitudinal data from an 8-week RCT.

SETTING: Tertiary academic center.

PARTICIPANTS: 63 adults with obesity (56% females, age 33.7±6.3 years) of whom 61 were randomized 1:1 to 8-weeks IN OXT (24 IU) four times daily or placebo.

INTERVENTION: Standardized meal, IN OXT vs. placebo.

MAIN OUTCOME MEASURE: AVP levels before and 30, 60, and 120 minutes after a standardized meal at baseline, and weeks 4, 6 and 8 after starting OXT or placebo.

RESULTS: In response to food intake, AVP levels decreased at 60 min (adjusted mean ± standard error = 68.55 ± 9.64 pg/mL) compared to fasting (80.99 ± 11.22 pg/mL; p=0.022). AVP levels did not significantly change over the course of 8-week IN OXT treatment vs. placebo (p≥0.544). There was no effect of body mass index (p≥0.615) or sex (p≥0.498) on AVP levels.

CONCLUSION: AVP levels decreased after food intake in adults with obesity, indicating a potential disruption in AVP signaling and possibly underlying obesity pathophysiology. Chronic IN OXT administration did not alter AVP levels, supporting safety of OXT-based therapeutics.

PMID:40314146 | DOI:10.1210/clinem/dgaf237