Intranasal Oxytocin for Obesity

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.).

Figure 1.. CONSORT Diagram.

Figure 2.. Effects of Intranasal Oxytocin (24IU Four Times Daily) versus Placebo on the Primary End Point Body Weight.

Displayed are the individual changes in body weight (kilograms) from baseline to week 8 among all participants of the modified intention-to-treat cohort with available data at both time points (oxytocin group: n=29, placebo group: n=22). Note that change in body weight had a value of zero for one participant of the control group and that for this participant, the assigned space does not show a bar. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; difference, −0.06 kg; 95% confidence interval, −1.4 to 1.3; P=0.934).

Figure 3.. Effects of Intranasal Oxytocin (24 IU Four Times Daily) versus Placebo on the Key Secondary End Points.

Displayed are the individual changes in total fat mass (Panel A), abdominal visceral adipose tissue (Panel B), liver fat fraction (Panel C), and resting energy expenditure (Panel D) from baseline to week 8 and caloric intake at an experimental test meal (Panel E) from baseline to week 6 among all participants of the modified intention-to-treat cohort with available data at both time points (total fat mass and resting energy expenditure: oxytocin group: n=29, placebo group: n=22; abdominal visceral adipose tissue: oxytocin group: n=28, placebo group: n=19; liver fat fraction: oxytocin group: n=25, placebo group: n=19; caloric intake at an experimental test meal: oxytocin group: n=29, placebo group: n=24). Note that change in caloric intake at an experimental test meal had a value of zero for one participant of the control group and that for this participant, the assigned space does not show a bar. Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference, 196.0 g; 95% confidence interval [CI], −1036 to 1428; abdominal visceral adipose tissue: difference, 3.1 cm²; 95% CI, −11.0 to 17.2; liver fat fraction: difference, −0.01; 95% CI, −0.03 to 0.01; resting energy expenditure: difference, −64.0 kcal/day; 95% CI, −129.3 to 1.4). Oxytocin compared with placebo was associated with reduced caloric intake at the experimental test meal from baseline to week 6 (−31.4 vs. 120.6 kcal; difference, −152.0 kcal; 95% CI, −302.3 to −1.7). The analyses of the secondary outcomes did not include a provision for correction for multiplicity. Therefore, the results should not be used to infer treatment effects.