SUN-221 Effects of Liraglutide on Obesity-Associated Functional Hypogonadism in Men: A Randomized, Testosterone Replacement Treatment-Controlled Study

Objective: Obesity causes functional hypogonadism(FH) due to suppression of hypothalamus-pituitary-testicular (HPT) axis that is potentially reversible. Weight reduction with lifestyle measures (LSM) should be recommended as a first line treatment approach. In clinical practice, LSM often fails and may be insufficient to relieve symptoms of FH. A role of testosterone replacement treatment (TRT), after a trail of unsuccessful LSM, is unclear. In selected patients, TRT could be started concomitantly or in addition to LSM to augment the benefits of LSM, although the quality of evidence supporting this concept is low. GLP-1 receptor agonist liraglutide is linked to progressive and sustained weight loss. Furthermore, a potential direct impact of GL-P1 agonism on hypothalamus-pituitary-testicular (HPT) axis was reported in preclinical models. Despite the fact, that the prevalence of FH in obese men is high, the impact of liraglutide on FH in obese men with or without diabetes has not yet been addressed in a randomized prospective clinical study. Aim: We aimed to compare the effects of liraglutide and TRT on FH in obese men that had been poor responders to LSM, by means of reversal of FH and weight reduction. Design:We designed 16-week prospective randomized open-label studywith 30 men (aged 46.5±10.9years, BMI 41.2±8.4 kg/m2, mean ± SD) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT). Methods: Sexual function with standardized questionnaires and anthropometric measures were assessed. A fasting blood was drawn for determination of endocrine and metabolic parameters followed by OGTT. Model-derived parameters including HOMA(IR)and calculated free testosterone (cFT) were calculated.Results: Total testosterone (+5.9±7.2 in TRT vs +2.6±3.5 nmol/l in LIRA) and the sexual function significantly increased in both arms, with no significant between treatment differences. SHBG tended to increase in LIRA. There was a significant differential effect on HPT axis resulting in further suppression of LH and FSH in TRT and a significant increase of LH and FSH in LIRA (p<0.001). Subjects treated with LIRA lost on average 7.9±3.8 kg compared with a 0.9±4.5 kg loss in TRT (P<0.001). LIRA was also superior in reduction of waist circumference. Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT.Conclusions: When LSM fails and bariatric surgery is not yet indicated, anti-obesity treatment with liraglutide should be advised over TRT, by means of overall health benefit improvement in men with obesity-associated FH. Future studies should investigate the complex crosstalk between GLP-1 and HPT axis beyond the mere impact of the magnitude of weight reduction.