Obesity, type 2 diabetes, and therapeutic weight loss are all associated with impaired bone quantity and microarchitecture. Glucagon-like peptide receptor analogs (GLP1RAs) have direct beneficial effects on bone microarchitecture, in preclinical settings. This study aimed to evaluate the net impact of GLP1RA on microarchitecture in overweight/obese type 2 diabetes individuals. It was an interventional, paired-sample cohort study with oral semaglutide in consecutive type 2 diabetes patients with overweight/obesity and metabolic-dysfunction associated steatotic liver disease. Oral semaglutide was initiated at 3 mg daily, with escalation to 14 mg at the end of 12 weeks. Bone turnover markers (P1NP, β-CTX) were estimated by electrochemiluminescence and body composition by DXA. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed using HRpQCT (XtremeCT II, Scanco Medical). There were 36 patients (44% males) with a mean (± SD) age of 50.8 ± 10.1 years, mean BMI of 34.3 ± 6.2 kg/m2 and median duration of diabetes being 7 (IQR 2-13) years. At 52 weeks, there was an increase in tibial total vBMD (317.4 ± 47.4 vs. 331.6 ± 52.7 mg HA/cm3, p = 0.06) and cortical vBMD at both radius and tibia (trend towards significance). Trabecular vBMD and trabecular bone volume fraction at radius were also increased. Males showed significantly increased tibial total and cortical vBMD, and trabecular bone volume fraction, but there was no significant change in females. There were no significant differences in bone microarchitecture based on steatosis or fibrosis reduction. Oral semaglutide improves vBMD in overweight/obese type 2 diabetes, despite a significant reduction in body weight.
Keywords: Bone microarchitecture; Glucagon-like peptide receptor analogs; HRpQCT; MASLD; Obesity; Semaglutide; Weight loss.
© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.