Primerjava učinkov semaglutida ali testosterona undekanoata na presnovne in endokrine kazalnike pri osebah z debelostjo, sladkorno boleznijo tipa 2 in funkcionalnim hipogonadizmom

Gregorič, Nadan (author), Jensterle Sever, Mojca (mentor), Janež, Andrej (comentor)

Uvod: Funkcionalni hipogonadizem pogosto prizadane moške s sladkorno boleznijo tipa 2 in debelostjo. Nadomestno zdravljenje s testosteronom pomembno izboljša simptome hipogonadizma in raven testosterona, vendar lahko negativno vpliva na spermatogenezo. Učinki agonistov receptorjev glukagonu podobnega peptida 1 na sladkorno bolezen tipa 2 in debelost so znani, na funkcionalni hipogonadizem pa še ne dovolj raziskani. Namen raziskave je primerjati učinke zdravljenja semaglutidom in s testosteronom undekanoatom na endokrine in presnovne parametre, okus in prehranjevalno vedenje pri moških s funkcionalnim hipogonadizmom, sladkorno boleznijo tipa 2 in debelostjo. Metode: Opravili smo randomizirano, odprto, klinično raziskavo pri 25 moških starih 50 let (46,1; 59,7) s sladkorno boleznijo tipa 2, debelostjo in funkcionalnim hipogonadizmom. Zdravili smo jih s semaglutidom subkutano ali testosteronom undecanoatom intramuskularno v obdobju 24 tednov. Ob randomizaciji in ob zaključku smo določili endokrinološke parametre, ocenili simptome hipogonadizma, napravili analizo semenske tekočine, izvedli preizkus okušanja, ocenili prehransko vedenje in opravili biopsijo podkožnega maščevnega tkiva. Rezultati: Raven celokupnega testosterona se je v obeh skupinah statistično značilno povečala, v skupini zdravljeni s testosteronom za 6,9 nmol/L (2,3; 12,1), v skupini zdravljeni s semaglutidom 1,6 nmol/L (0,7; 8,2), oba p < 0,05. V skupini s testosteronom je bila razlika statistično značilno večja (p < 0,002). Zdravljenje s semaglutidom je statistično značilno povečalo število morfološko normalnih semenčic (relativna sprememba 0,37 (0,21; 0,88), p = 0,012), zdravljenje s testosteronom pa zmanjšanjšalo koncentracijo (relativna sprememba -0,67 (-0,88; -0,54), p = 0,028) in celokupo število semenčic (relativna sprememba -0,59 (-0,87; 0,50), p = 0,018). V obeh skupinah je prišlo do statistično značilnega izboljšanja simptomov ocenjenih z vprašalnikom simptomi staranja pri moških (oba p < 0,05), razlik med skupinama ni bilo (p > 0,05). Spolna funkcija, ocenjena z mednarodnim indeksom erektilne funkcije 15, se je statistično značilno izboljšala le v skupini zdravljeni s testosteronom (p < 0,05). Zaznava okusa se ni spremenila v nobeni od skupin (vsi p < 0,05). Le v skupini s semaglutidom je bilo manj nenadzorovanega prehranjevanja (p < 0,05). V nobeni od skupin ni prišlo do spremembe izražanja informacijske ribonukleinske kisline za glukozni prenašalec 4 v podkožnem maščobnem tkivu (p > 0,05). Zaključek: Zdravljenje s semaglutidom je pomembno izboljšalo koncentracijo celokupnega tesotsterona ter izboljšalo simptome hipogonadizma, vendar manj izrazito kot zdravljenje s testosteronom. Za razliko od testosterona je imel semaglutid ugoden učinek na kakovost semenske tekočine.

• Language: Slovenian
• Keywords: funkcionalni hipogonadizem, debelost, sladkorna bolezen, semaglutid, GLP-1 RA, testosteron, semenska tekočina
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2025
• PID: 20.500.12556/RUL-170286
• Publication date in RUL: 03.07.2025

Secondary language

• Language: English
• Title: The comparison of the effects of semalgutide or testosterone undecanoate on metabolic and dneocirne indicators in subjects with obesity, type 2 diabetes mellitus and functional hypogonadism

Abstract

Introduction: Functional hypogonadism frequently affects men with type 2 diabetes and obesity. Testosterone replacement therapy significantly improves symptoms of hypogonadism and testosterone levels but may negatively impact spermatogenesis. The effects of glucagon-like peptide-1 receptor agonists on type 2 diabetes and obesity are well established, but their impact on functional hypogonadism remains insufficiently studied. The aim of this study was to compare the effects of treatment with semaglutide and testosterone undecanoate on endocrine and metabolic parameters, taste perception, and eating behavior in men with functional hypogonadism, type 2 diebetes, and obesity. Methods: We conducted a randomized, open-label clinical trial in 25 men aged 50 years (46,1; 59,7) with type 2 diabetes, obesity, and functional hypogonadism. They were treated with subcutaneous semaglutide or intramuscular testosterone undecanoate over 24 weeks. Endocrine parameters were assessed at randomization and study completion, hypogonadism symptoms were evaluated, semen analysis was performed, a taste perception test was conducted, eating behavior was assessed, and a biopsy of subcutaneous adipose tissue was obtained. Results: Total testosterone levels significantly increased in both groups, in testosterone group 6,9 nmol/L (2,3; 12,1); in semaglutide group 1,6 nmol/L (0,7; 8,2)), with a significantly greater increase in the testosterone group (p < 0,002). Treatment with semaglutide significantly increased the number of morphologically normal sperm (relative change: 0,37 (relative change 0,21; 0,88), p = 0,012), while testosterone therapy significantly reduced sperm concentration (relative change -0,67 (-0,88; -0,54), p = 0,028) and total sperm count (relative change -0,59 (-0,87; -0,50), p = 0,018). Both groups showed significant improvement in hypogonadism symptoms assessed with Aging males' symptoms questionnaire (both p < 0,05), with no differences between them (p > 0,05). Sexual function, assessed with International Index of erectile function 15 questionnaire, significantly improved only in the testosterone-treated group (p < 0,05). Taste perception did not change in either group (all p > 0,05). Only in the semaglutide group was a reduction in uncontrolled eating observed (p < 0,05). No changes in expression of messenger ribonucleic acid for glucose transporter type 4 in subcutaneous adipose tissue were detected in either group (p > 0,05). Conclusion: Treatment with semaglutide significantly improved total testosterone concentration and alleviated hypogonadism symptoms, though less pronounced than testosterone therapy. Unlike testosterone, semaglutide had a beneficial effect on semen quality.

• Keywords: functional hypogonadism, obesity, diabetes mellitus, semaglutide, GLP-1 RA, testosterone, semen