Intranasal Oxytocin for Obesity. — VialBase Research

Summary

Preclinical and preliminary translational work had suggested that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss — the entire scientific premise behind selling intranasal oxytocin as a weight management tool. This randomized, double-blind, placebo-controlled trial tested that premise directly in humans. Sixty-one adults with obesity (54% women; mean age 33.6 ± 6.2 years; mean BMI 36.9 ± 4.9) were randomly assigned 1:1, stratified by sex and obesity class, to intranasal oxytocin 24 IU or placebo four times daily for 8 weeks. The primary endpoint was change in body weight from baseline to week 8, with key secondary endpoints covering body composition (total fat mass, abdominal visceral adipose tissue, liver fat fraction), resting energy expenditure adjusted for lean mass, and caloric intake at an experimental test meal. The trial was unambiguously negative on its primary endpoint: body weight change did not differ between groups (0.20 kg with oxytocin vs. 0.26 kg with placebo; P=0.934). Nor was oxytocin associated with beneficial effects on any measure of body composition or on resting energy expenditure — the confidence interval for resting energy expenditure (−64.0 kcal/day; 95% CI, −129.3 to 1.4) points if anything in the wrong direction. The single positive finding was acute and narrow: oxytocin reduced caloric intake at one experimental test meal by 152.0 kcal versus placebo (95% CI, −302.3 to −1.7), an effect that plainly did not accumulate into any change in weight or fat over eight weeks. There were no serious adverse events, and adverse event incidence and severity did not differ between groups.

Key Findings

• 61 adults with obesity randomized 1:1 to intranasal oxytocin 24 IU or placebo, four times daily for 8 weeks (ClinicalTrials.gov NCT03043053), stratified by sex and obesity class
• Primary endpoint failed: no difference in body weight change from baseline to week 8 (0.20 kg oxytocin vs. 0.26 kg placebo; P=0.934)
• No beneficial effect on body composition — total fat: 196.0 g (95% CI, −1036 to 1428); visceral adipose tissue: 3.1 cm² (95% CI, −11.0 to 17.2); liver fat fraction: −0.01 (95% CI, −0.03 to 0.01)
• No beneficial effect on resting energy expenditure adjusted for lean mass: −64.0 kcal/day (95% CI, −129.3 to 1.4) — the opposite direction from the preclinical hypothesis of increased energy expenditure
• Oxytocin did reduce caloric intake at a single experimental test meal at week 6 (−31.4 kcal vs. +120.6 kcal for placebo; difference −152.0 kcal; 95% CI, −302.3 to −1.7), demonstrating an acute appetite effect with no durable metabolic consequence
• Safety was unremarkable: no serious adverse events, and incidence and severity of adverse events did not differ between oxytocin and placebo
• Authors’ conclusion, stated plainly: intranasal oxytocin four times daily for 8 weeks did not reduce body weight in adults with obesity

Relevance to Oxytocin

This is the study that settles the weight-loss question for Oxytocin, and it should be quoted rather than paraphrased: intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. The trial used the same route, a standard 24 IU dose, and an aggressive four-times-daily schedule — it is not a case of underdosing or an inadequate protocol. Every downstream marketing claim built on the preclinical rodent literature (reduced intake, raised energy expenditure, fat loss) was tested here and came back null, with the resting energy expenditure estimate actually trending the wrong way. The one real effect — eating about 152 fewer calories at a single supervised test meal — is a useful illustration of why acute laboratory findings do not equal clinical benefit: that effect was measurable and yet produced no weight, fat, visceral fat, or liver fat change over two months. Note also that oxytocin is an FDA-approved drug only for obstetric indications; intranasal use for weight, bonding, or social effects is off-label and, in the peptide market, unapproved. The reassuring safety profile here should not be read as endorsement of a use case this same trial disproved.

Citation

Plessow F, Kerem L, Wronski ML, et al. Intranasal Oxytocin for Obesity. NEJM evidence. 2024;3(5):EVIDoa2300349. doi:10.1056/EVIDoa2300349.

See Also

• Parent compound: Oxytocin