GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

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CONTEXT: Recent studies indicate that glucagon-like peptide 1 (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 reductions.

DESIGN: Randomized control study.

SETTING: Out-patient research hospital clinic.

PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), 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 (1.2mg/day) for 52 weeks. In case of weight gain, up to two meals per day could be substituted with a low-calorie diet product in order to maintain the weight loss.

MAIN OUTCOME MEASURES: Total, pelvic and arm-leg bone mineral content (BMC) and bone markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks 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<0.0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was 4 times greater in the control group compared to the liraglutide group (estimated difference 27g (95% CI 5-48), p=0.01), 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<0.05). The bone resorption marker CTX-1 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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number8
Pages (from-to)2909 –2917
Number of pages9
Publication statusPublished - 2015

ID: 138863038