Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study.

Background: Tirzepatide (TZP), a dual agonist of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has recently been introduced in Italy for the treatment of obesity. Obesity is frequently associated with metabolic hypogonadism, which is characterized by low testosterone levels and normal low levels of gonadotropin. This condition exacerbates metabolic dysfunction and increases the risk of type 2 diabetes mellitus (DM). This study aims to evaluate the effects of TZP on metabolic hypogonadism in patients with obesity.

Methods: Male patients with obesity and metabolic hypogonadism were enrolled. Exclusion criteria included recent use of medications for hypertension, dyslipidemia, DM, anti-androgens, or hyperprolactinemia. All participants followed a hypocaloric diet and engaged in 20 min of daily brisk walking. Patients were allocated to one of the following treatment groups: Group A received 2.5 mg of TZP weekly for the first month, with the dose increased to 5 mg from the second month; Group B received no pharmacological treatment: Group C received transdermal testosterone. Clinical evaluations were conducted at 2 months including assessment of body composition, the Binge Eating Scale (BES), 5-item International Index of Erectile Function (IIEF-5) questionnaire to evaluate erectile dysfunction (ED), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone (TT), and 17β-estradiol (E). Free (fT) and bioavailable testosterone (bioT) were calculated using the Vermeulen formula.

Results: A total of 83 patients with obesity (mean age 55.3 ± 5.5 years) were included in the study, divided into three groups: Group A (28 patients, mean age 56.3 ± 4.7 years), Group B (30 patients, mean age 55.1 ± 5.2 years), and Group C (25 patients, mean age 54.0 ± 6.5 years). At baseline, significant differences were observed in waist circumference (WC), which was higher in Group B, as well as in the BES score, lean mass (LM), and serum LH levels, all of which were higher in Group A. After 2 months, Group A showed significantly greater reductions in body weight, WC, BES score, and fat mass, along with a notable increase in LM and IIEF-5 score compared to Groups B and C. Additionally, Group A exhibited significantly higher serum levels of LH, FSH, SHBG, TT, fT, and bioT, while E levels were significantly lower than both Groups B and C.

Conclusion: The results of this study suggest that TZP is effective in improving both metabolic parameters, ED, and gonadal hormone levels in patients with obesity and metabolic hypogonadism. These findings position TZP as a promising treatment for obese patients with functional hypogonadism arising from metabolic-related alterations.