Skip to main content
NEJM Evidence homepage

This article is available to subscribers. Subscribe now.

Abstract

Background

Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity.

Methods

In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6.

Results

Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [−1036 to 1428]; visceral fat: 3.1 cm2 [−11.0 to 17.2]; liver fat: −0.01 [−0.03 to 0.01]; resting energy expenditure: −64.0 kcal/day [−129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (−31.4 vs. 120.6 kcal; difference [95% confidence interval], −152.0 kcal [−302.3 to −1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups.

Conclusions

In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.)

Go behind the scenes of clinical research.

Notes

A data sharing statement provided by the authors is available with the full text of this article.
Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant numbers R01DK1009932 and P30DK040561), the National Institute of Mental Health (grant number K24MH120568), and the National Center for Advancing Translational Sciences (grant number UL1TR001102).
Disclosure forms provided by the authors are available with the full text of this article.
We thank the trial participants, the members of our Data Safety and Monitoring Board, our trial staff members who supported data collection, and the staff at the Massachusetts General Hospital Clinical Research Center and Athinoula A. Martinos Center for Biomedical Imaging.

Supplementary Material

Protocol (evidoa2300349_protocol.pdf)
Supplementary Appendix (evidoa2300349_appendix.pdf)
Disclosure Forms (evidoa2300349_disclosures.pdf)
Data Sharing Statement (evidoa2300349_data-sharing.pdf)

Information & Authors

Information

Published In

History

Published online: April 23, 2024
Published in issue: April 23, 2024

Topics

Authors

Affiliations

Franziska Plessow, Ph.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Liya Kerem, M.D., M.S.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Division of Pediatric Endocrinology, Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem
Marie-Louis Wronski, M.S.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
Elisa Asanza, M.S.N., M.P.H.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Michelle L. O’Donoghue, M.D.
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston
Fatima C. Stanford, M.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Division of Pediatric Endocrinology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston
Kamryn T. Eddy, Ph.D.
Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston
Tara M. Holmes, M.S., R.D.
Translational and Clinical Research Centers, Massachusetts General Hospital and Harvard Medical School, Boston
Madhusmita Misra, M.D., M.P.H.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Division of Pediatric Endocrinology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston
Jennifer J. Thomas, Ph.D.
Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston
Francesca Galbiati, M.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Maged Muhammed, M.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Aluma Chovel Sella, M.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
The Jesse Z. and Sara Lea Shafer Institute of Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
Kristine Hauser, C.N.P.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Sarah E. Smith, D.N.P.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Katherine Holman
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Julia Gydus
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Anna Aulinas, M.D., Ph.D.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona
Mark Vangel, Ph.D.
Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston
Brian Healy, Ph.D.
Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston
Arvin Kheterpal, M.D.
Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston
Martin Torriani, M.D.
Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston
Laura M. Holsen, Ph.D.
Division of Women’s Health, Department of Medicine and Department of Psychiatry, Brigham and Women’s Hospital and Harvard Medical School, Boston
Miriam A. Bredella, M.D.
Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston
Elizabeth A. Lawson, M.D., M.M.Sc. [email protected]
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston

Notes

Dr. Lawson can be contacted at [email protected] or at 50 Staniford St., Suite 750B, Boston, MA 02114.
Drs. Plessow and Kerem contributed equally to this article.

Metrics & Citations

Metrics

Altmetrics

Citations

Export citation

Select the format you want to export the citation of this publication.

Cited by

  1. Oxytocin and Body Weight Homeostasis — Wrong Hypothesis or Wrong Methodology?, NEJM Evidence, 3, 5, (2024)./doi/full/10.1056/EVIDe2400072
    Abstract
Loading...

View Options

View options

PDF

View PDF

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

CONTENT LINK

Share

Sharpen your skills. Inform your decision-making.
Go behind the scenes of clinical research.

This article is available to subscribers. Subscribe now.