GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women
Abstract
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/m(2) 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.
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In euglycemic individuals, liraglutide increased procollagen type I N-terminal propeptide levels by 16%, compared with a 2% decrease in the placebo group.
“In euglycemic individuals, liraglutide increased procollagen type I N-terminal propeptide (P-PINP) levels by 16%, compared with a 2% decrease in the placebo group [42].”
From Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review (2025) · cites this paper as [42]
Treatment with liraglutide has been shown to increase bone formation in body weight-reduced obese women when compared to placebo.
“Treatment with liraglutide has been shown to increase bone formation in body weight-reduced obese women when compared to placebo (14).”
The reduction in PINP in the exenatide-treated group contrasts a previously reported increase of PINP in obese women after liraglutide treatment.
“The reduction in PINP in the exenatide-treated group contrasts a previously reported increase of PINP in obese women, who experienced a 12% body weight reduction after 12 months of liraglutide treatment (14).”
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- Authors
- Iepsen, E. W., Lundgren, J. R., Hartmann, B., Pedersen, O., Hansen, T., Jørgensen, N. R., Jensen, J.-E. B., Holst, J. J., Madsbad, S., & Torekov, S. S.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Iepsen, Eva W.
- Torekov, Signe S.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-08
- Volume
- 100
- Issue
- 8
- Pages
- 2909-2917
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1934495549
- Cited by
- 193
- References
- 54
- Citations by year
- 2026: 16 · 2025: 39 · 2024: 21 · 2023: 15 · 2022: 16 · 2021: 9 · 2020: 11 · 2019: 24 · 2018: 15 · 2017: 10 · 2016: 9 · 2015: 8
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish Diabetes Academy
- Ministério da Ciência, Tecnologia e Inovação
- Novo Nordisk
- Copenhagen Graduate School for Nanoscience and Nanotechnology
- Faculty of Health and Medical Sciences, University of Western Australia
- Hvidovre Hospital
- Novo Nordisk Fonden (NNF14OC0009787)
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- GLP-1 receptor agonists, liraglutide, bone loss, bone formation, weight loss, obesity, obese women, bone mineral content, bone turnover markers, P1NP, C-terminal telopeptide of type I collagen, hypocaloric diet, weight maintenance, glucagon-like peptide-1, osteoporosis prevention
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Adolescent, Adult, Aged, Bone Resorption, Female, Humans, Middle Aged, Obesity, Osteogenesis, Weight Loss, Receptors, Glucagon, Caloric Restriction, Glucagon-Like Peptide 1, Young Adult
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