Effect of GLP1Ra Therapy on Bone Mineral Density and Turnover in Overweight/Obese Older Adults with Prediabetes or Type 2 Diabetes: Post Hoc Analysis of a 20-Week Pilot Trial

Lauren Dinkla¹Kristen M. Beavers^1,2Ronna Robbins³Dela Akpalu⁴Sarah J. Wherry^5,6Gary Miller¹Daniel P. Beavers⁴Sara Espinoza^7,8,9Jonathan Trejo¹⁰Allison Stepanenko⁹Tiffany Cortes^10,9*

• ¹Wake Forest University Department of Health & Exercise Science, Winston-Salem, United States
• ²Wake Forest School of Medicine Department of Internal Medicine, Winston-Salem, United States
• ³Texas Woman's University Department of Nutrition and Food Sciences, Denton, United States
• ⁴Wake Forest University Department of Statistical Science, Winston-Salem, United States
• ⁵University of Colorado Anschutz Medical Campus Division of Geriatric Medicine, Aurora, United States
• ⁶VA Eastern Colorado Geriatric Research, Education, and Clinical Center, Aurora, United States
• ⁷Cedars-Sinai Medical Center Department of Medicine Center for Translational Geroscience, Los Angeles, United States
• ⁸Cedars-Sinai Medical Center Department of Medicine Diabetes and Aging Center, Los Angeles, United States
• ⁹The University of Texas Health Science Center at San Antonio Sam and Ann Barshop Institute for Longevity and Aging Studies, San Antonio, United States
• ¹⁰San Antonio Geriatric Research, Education, and Clinical Center, San Antonio, United States

The purpose of this exploratory post-hoc analysis was to study the impact of semaglutide on measures of bone health in older adults. Data came from a 20-week pilot trial (NCT05786521) which randomized 20 older adults (72.7±4.8 years of age, 50% women, 45% Hispanic) living with prediabetes/diabetes (hemoglobin A1C 5.7%-7.5%) and overweight/obesity (BMI: 32.9±4.0 kg/m2) to 1.0 mg/weekly semaglutide+lifestyle counseling (n=10) or lifestyle counseling alone (n=10). Total body weight, bone mineral density (BMD), and bone turnover markers (BTMs) [C-terminal telopeptide of type 1 collagen (CTX), and procollagen type I N-propeptide (P1NP)] were measured at baseline and 20 weeks. 20-week weight loss was greater in the semaglutide+lifestyle counseling group than lifestyle counseling alone (-5.3% vs -0.89%; p<0.01). No significant differences in whole body BMD (p=0.77) or BTMs (CTX: p=0.56, P1NP: p=0.78) were observed between groups over time. In this 20-week pilot trial, we did not find evidence to suggest that weight loss achieved with semaglutide was associated with change in BMD or BTMs in older adults. Notably, the observed differences showed consistently lower BMD and higher bone turnover at follow-up in the semaglutide+lifestyle group compared to lifestyle alone. Additional work in this area is warranted to further evaluate the effect of GLP1Ra use on skeletal health outcomes in older adults given the pilot nature of the trial, the small degree of weight loss achieved, and the well-described association between weight loss and fracture risk.