Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study

BackgroundType 2 diabetes mellitus (T2DM) is an independent risk factor for osteoporosis, increasing the risk of fractures and poor prognosis. Recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may play a protective role in bone metabolism. However, limited evidence ex...

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Main Authors: Ming Chen, Yiming Lyu, Jingwei Zhao, Xianwei Han, Tao Huang, Tongtao Yang, Yong Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1586589/full
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author Ming Chen
Yiming Lyu
Jingwei Zhao
Xianwei Han
Tao Huang
Tongtao Yang
Yong Zhou
author_facet Ming Chen
Yiming Lyu
Jingwei Zhao
Xianwei Han
Tao Huang
Tongtao Yang
Yong Zhou
author_sort Ming Chen
collection DOAJ
description BackgroundType 2 diabetes mellitus (T2DM) is an independent risk factor for osteoporosis, increasing the risk of fractures and poor prognosis. Recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may play a protective role in bone metabolism. However, limited evidence exists on their effect on osteoporosis incidence in T2DM patients. This study aimed to evaluate the association between GLP-1 RA use and osteoporosis risk in a real-world cohort of elderly T2DM patients.MethodsThis retrospective cohort study utilized electronic medical records (EMRs) from Tangdu Hospital, Xi’an, China, between January 1, 2012, and December 31, 2023. Patients with T2DM who had at least two clinical visits annually and no prior osteoporosis diagnosis (ICD-10: M80-M82) at baseline were included. The primary outcome was the incidence of osteoporosis during follow-up. Cox proportional hazards models were used to evaluate the association between GLP-1 RA use and osteoporosis risk, adjusting for age, sex, BMI, blood pressure, lipid profile, renal function, osteocalcin, vitamin D levels, HbA1c, statin use, antihypertensive medication use, and smoking status. Subgroup analyses were conducted to assess potential effect modifications.ResultsA total of 1,845 patients with T2DM were included, of whom 676 (36.6%) developed osteoporosis during follow-up. Among the 256 patients who received GLP-1 RAs, the incidence of osteoporosis was significantly lower than in those who did not receive GLP-1 RAs (P < 0.01). In the fully adjusted Cox model, GLP-1 RA use was associated with a significantly reduced risk of osteoporosis compared to non-users (hazard ratio [HR] = 0.69, 95% confidence interval [CI] =0.45-0.84, P < 0.05). Subgroup analyses indicated that the protective effect of GLP-1 RAs was consistent across age, sex, BMI, smoking status, and antihypertensive medication use (P for interaction > 0.05).ConclusionIn patients with T2DM, patients with treatment of GLP-1 RAs resulted in lower risks of osteoporosis than those without treatment of GLP-1 RAs. These findings support the potential bone-protective effects of GLP-1 RAs but further randomized controlled trials (RCTs) or large-scale database analyses are needed to confirm these observations and guide clinical recommendations.
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spelling doaj-art-a9b479fd6cec480bbcd0a9486284b81d2025-08-20T03:13:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-05-011610.3389/fendo.2025.15865891586589Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world studyMing Chen0Yiming Lyu1Jingwei Zhao2Xianwei Han3Tao Huang4Tongtao Yang5Yong Zhou6Department of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaMedmotion Clinic, Shanghai, ChinaDepartment of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaDepartment of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaDepartment of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaDepartment of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaDepartment of Orthopedics, Tangdu Hospital, Airforce Medical University (Fourth Military Medical University), Xi’an, Shanxi, ChinaBackgroundType 2 diabetes mellitus (T2DM) is an independent risk factor for osteoporosis, increasing the risk of fractures and poor prognosis. Recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may play a protective role in bone metabolism. However, limited evidence exists on their effect on osteoporosis incidence in T2DM patients. This study aimed to evaluate the association between GLP-1 RA use and osteoporosis risk in a real-world cohort of elderly T2DM patients.MethodsThis retrospective cohort study utilized electronic medical records (EMRs) from Tangdu Hospital, Xi’an, China, between January 1, 2012, and December 31, 2023. Patients with T2DM who had at least two clinical visits annually and no prior osteoporosis diagnosis (ICD-10: M80-M82) at baseline were included. The primary outcome was the incidence of osteoporosis during follow-up. Cox proportional hazards models were used to evaluate the association between GLP-1 RA use and osteoporosis risk, adjusting for age, sex, BMI, blood pressure, lipid profile, renal function, osteocalcin, vitamin D levels, HbA1c, statin use, antihypertensive medication use, and smoking status. Subgroup analyses were conducted to assess potential effect modifications.ResultsA total of 1,845 patients with T2DM were included, of whom 676 (36.6%) developed osteoporosis during follow-up. Among the 256 patients who received GLP-1 RAs, the incidence of osteoporosis was significantly lower than in those who did not receive GLP-1 RAs (P < 0.01). In the fully adjusted Cox model, GLP-1 RA use was associated with a significantly reduced risk of osteoporosis compared to non-users (hazard ratio [HR] = 0.69, 95% confidence interval [CI] =0.45-0.84, P < 0.05). Subgroup analyses indicated that the protective effect of GLP-1 RAs was consistent across age, sex, BMI, smoking status, and antihypertensive medication use (P for interaction > 0.05).ConclusionIn patients with T2DM, patients with treatment of GLP-1 RAs resulted in lower risks of osteoporosis than those without treatment of GLP-1 RAs. These findings support the potential bone-protective effects of GLP-1 RAs but further randomized controlled trials (RCTs) or large-scale database analyses are needed to confirm these observations and guide clinical recommendations.https://www.frontiersin.org/articles/10.3389/fendo.2025.1586589/fulltype 2 diabetesosteoporosisGLP-1 receptor agonistselectronic medical recordscohort studybone metabolism
spellingShingle Ming Chen
Yiming Lyu
Jingwei Zhao
Xianwei Han
Tao Huang
Tongtao Yang
Yong Zhou
Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
Frontiers in Endocrinology
type 2 diabetes
osteoporosis
GLP-1 receptor agonists
electronic medical records
cohort study
bone metabolism
title Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
title_full Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
title_fullStr Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
title_full_unstemmed Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
title_short Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study
title_sort use of glp 1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes a real world study
topic type 2 diabetes
osteoporosis
GLP-1 receptor agonists
electronic medical records
cohort study
bone metabolism
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1586589/full
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