Endocrine Abstracts

JOINT1038

Background: In animal studies, systemic and central injections of GLP-1 were found to increase plasma oxytocin concentrations. Additionally, recent rodent research revealed that 70% of GLP-1 receptor-positive neurons in the paraventricular nucleus also expressed oxytocin receptors. When oxytocin and GLP-1 were co-administered systemically, there was a significant increase in action potential firing in oxytocin-receptor-positive neurons in the paraventricular nucleus. Based on these findings, considering the functional and anatomical proximity as well as the synergistic effects, we hypothesized that dulaglutide may modulate and increase oxytocin plasma levels in humans.

Methods: This is a secondary analysis of a randomized, double-blind, placebo-controlled crossover trial of healthy eugonadal men, age 18-50 years with active and satisfactory sex lives that examined the effect of the GLP-1 RA dulaglutide on sexual desire as a primary endpoint. Participants were randomly assigned (1:1) to receive either dulaglutide or placebo for four weeks. Oxytocin plasma levels were measured repetitively in a standardized manner, with three samples taken every 15 minutes at baseline and at the evaluation visit. We used the mean of these three measurements for our analysis. Changes within individuals were then compared after four weeks of treatment with the GLP-1 receptor agonist dulaglutide vs placebo using paired t-tests.

Findings: The median [IQR] age of participants at inclusion was 24.5 [21.0, 29.0] years, and the median BMI was 23.85 [22.15, 25.00]. Mean (SD) oxytocin baseline levels were comparable between groups: 50.6 pq/ml (17.0) in the treatment group and 50.5 pq/ml (18.2) in the placebo group. After 4 weeks of treatment with dulaglutide and placebo oxytocin concentrations remained stable and were 53.2 pq/ml (12.7) and 50.5 pq/ml (17.8), respectively. Mean (SD) change from baseline in oxytocin concentrations was + 2.6 pq/ml (21) in the treatment group and 0.0 pq/ml (19.4) in the placebo group. The estimated difference between the two treatment was: 2.58 [95% CI −12.9, 18.4]. InterpretationOur study found no significant change in oxytocin plasma levels following a four-week treatment with dulaglutide vs placebo. Differences in results compared to animal data may be due to lower dosing, central vs peripheral administration, choice of GLP-1 RA, or acute vs chronic use. In addition, whether the results would be different in women or in people with obesity/diabetes mellitus, where altered GLP-1 metabolism is expected, needs to be investigated in future studies. FundingSwiss National Science Foundation (PZ00P3_193206), Gottfried and Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation.