Fezolinetant and Tirzepatide Show Promise While Testosterone Fails to Cut Fracture Risk

New findings from several pivotal studies in endocrinology were presented at the American College of Physicians Internal Medicine Meeting 2025, offering important clinical updates for internists. Irl Hirsch, MD, MACP, professor of medicine at the University of Washington Diabetes Institute, highlighted several studies, including those that examined the effectiveness of fezolinetant in managing vasomotor symptoms of menopause, the unexpected fracture outcomes in testosterone therapy for hypogonadal men, and a 93% risk reduction in type 2 diabetes progression with tirzepatide in individuals with prediabetes.

Given the growing gap in endocrinology care across the United States—with nearly 70% of counties lacking an endocrinologist—internists are increasingly called upon to manage a wider range of endocrine conditions. This update underscores relevant research to aid that responsibility, emphasizing therapies with immediate clinical implications.

“Internists will by necessity need to see more diabetes and general endocrinology than in past eras,” the presenter wrote.

In a BMJ study, fezolinetant, a non-hormonal neurokinin 3 receptor antagonist, was shown to significantly reduce vasomotor symptoms in menopausal women unsuitable for hormone therapy. During a 6-month period, patients reported improved sleep and global impression scores alongside a statistically significant decrease in symptom frequency and severity.

Meanwhile, the TRAVERSE trial evaluated testosterone therapy in more than 5000 hypogonadal men. Contrary to expectations, testosterone treatment did not lower clinical fracture incidence compared with placebo. Most observed fractures in the testosterone group were attributed to trauma-related injuries such as ankle and rib fractures, possibly reflecting increased physical activity rather than bone fragility. Typical osteoporotic fractures showed no group differences.

The SURMOUNT-4 trial examined the impact of tirzepatide in 2539 individuals with obesity, including 1032 with prediabetes. During 176 weeks, tirzepatide demonstrated a 93% risk reduction in the progression to type 2 diabetes, marking a significant preventive milestone.

Each study presented has its own limitations. For instance, the testosterone trial did not account for behavioral confounding in physical activity, and the tirzepatide study, while long-term, focuses on surrogate outcomes rather than hard clinical endpoints like mortality.

Reference:
Hirsch IB. Update in Endocrinology. Presented at: American College of Physicians Internal Medicine Meeting; April 3-5, 2025; New Orleans, LA. Accessed March 28, 2025. https://annualmeeting.acponline.org/educational-program/scientific-program/scientific-sessions