Semaglutide use tied to neuromuscular junction degradation in older adults with T2DM

Older men with type 2 diabetes mellitus (T2DM) may experience a decrease in muscle strength and physical performance following treatment with semaglutide, possibly caused by neuromuscular junction degradation and neuronal damage, a study has found.

Some 141 older men with T2DM received either semaglutide (n=68) or sitagliptin (n=73) and underwent assessments at baseline, 6 months, and 1 year.

The researchers then measured handgrip strength (HGS), gait speed, appendicular skeletal muscle mass index (ASMI), short physical performance battery (SPPB), and plasma concentrations of C-terminal agrin fragment (CAF22), neurofilament light chain (NfL), and brain-derived neurotrophic factor (BDNF).

Participants in the semaglutide group showed significant reductions in HGS, gait speed, ASMI, and SPPB scores (p<0.05 for all) during the study period. They also had more pronounced increases in plasma CAF22 and NfL levels than those treated with sitagliptin (p<0.05 for all).

In general, higher CAF22 and NfL levels in older men taking semaglutide were associated with poorer HGS, ASMI, and SPPB scores. On the other hand, lower BDNF levels correlated with reduced ASMI and SPPB at specific time points (p<0.05 for all).

In multiple regression analysis, CAF22 showed a significantly negative association with NfL, while BDNF was positively associated with sarcopenia parameters, particularly among participants in the semaglutide group.

“These findings underscore the importance of closely monitoring musculoskeletal health in patients receiving semaglutide,” the researchers said.