Effects of liraglutide on obesity-associated functional hypogonadism in men

Abstract

Lifestyle measures (LSMs) should be the first-line approach offered for obesity-related functional hypogonadism (FH). When LSMs fail, the role of testosterone replacement treatment (TRT) is unclear. GLP1 receptor agonist liraglutide is linked to progressive and sustained weight loss. A potential direct impact of GLP1 on hypothalamus-pituitary-testicular (HPT) axis was reported in animal models. 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. We designed a 16-week prospective randomized open-label study with 30 men (aged 46.5 ± 10.9 years, BMI 41.2 ± 8.4 kg/m2, mean ± s.d.) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT). Sexual function and anthropometric measures were assessed. Fasting blood was drawn for determination of endocrine and metabolic parameters followed by OGTT. Model-derived parameters including HOMAIR and calculated free testosterone (cFT) were calculated. Total testosterone significantly increased in both arms (+5.9 ± 7.2 in TRT vs +2.6 ± 3.5 nmol/L in LIRA) and led to improved sexual function. LIRA resulted in a significant increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P < 0.001 for between-treatment effect). 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). Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT. Liraglutide was superior to TRT in improving an overall health benefit in men with obesity-associated FH after LSM failed.

Treatment of Functional Hypogonadism Besides Pharmacological Substitution

“…Only one study investigated the effect of an antiobesity drug, i.e., liraglutide, on HPT in obese hypogonadal men with sexual symptoms and poor responses to lifestyle measures [49]. Liraglutide is a glucagon-like peptide-1 receptor agonist first approved for treatment of T2DM at doses up to 1.8 mg/d and later on approved for weight loss at a higher dosage (3.0 mg/d).…”

“…Liraglutide is a glucagon-like peptide-1 receptor agonist first approved for treatment of T2DM at doses up to 1.8 mg/d and later on approved for weight loss at a higher dosage (3.0 mg/d). In this trial [49], effects of liraglutide on TT levels were compared to those of TTh (1% T gel) in a 16-week study with 15 subjects enrolled per arm. Liraglutide, but not TTh, induced a 6% reduction in weight.…”

Metabolic Disorders and Male Hypogonadotropic Hypogonadism

“…These results suggest that antidiabetic drugs with a differential effect on body weight, namely, drugs which increase or reduce body weight, might consistently display a differential effect on androgenic status; nevertheless, scant literature exists investigating the effects of the new classes of antidiabetic drugs with a positive or neutral effect on body weight on testosterone levels. One study on 30 men with obesity-associated hypogonadism demonstrated that liraglutide administered for 16 weeks at a daily dose of 0.6 mg, and weekly titrated up to 3 mg, significantly increased gonadotropins and TT levels (105). Moreover, a different study on 45 obese and diabetic hypogonadal men demonstrated that adding liraglutide to lifestyle changes, metformin and testosterone treatment, in patients with insufficient metabolic control, significantly increased testosterone levels until normalization by means of improved body weight and glycemic control (106).…”

Male health and obesity – diagnostic and therapeutic approach

“…На фоне терапии лираглутидом вес снизился в среднем на 7,9 кг, а в группе тестостерона вес практически не изменился --0,9 кг (P<0,001). Уровни гонадотропинов увеличились в группе лираглутида 3 мг, в отличие от снижения, которое наблюдалось при проведении терапии тестостероном [58].…”