GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women

Context: Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. Objective: To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. Design: Randomized control study. Setting: Outpatient research hospital clinic. Participants: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m2 and age 46 ± 2 years. Intervention: After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. Main Outcome Measures: Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. Results: Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P < .0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group (estimated difference, 27 g; 95% confidence interval, 5–48; P = .01), although the 12% weight loss was maintained in both groups. In the liraglutide group, the bone formation marker P1NP increased by 16% (7 ± 3 μg/L) vs a 2% (−1 ± 4 μg/L) decrease in the control group (P < .05). The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase. Conclusions: Treatment with a long-acting GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.