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Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis

PURPOSE: Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Embase, Medline, ClinicalTrials.gov,...

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Autores principales: Zhang, Yu-Sheng, Zheng, Yan-Dan, Yuan, Yan, Chen, Shi-Chun, Xie, Bao-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553257/
https://www.ncbi.nlm.nih.gov/pubmed/34721294
http://dx.doi.org/10.3389/fendo.2021.735824
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author Zhang, Yu-Sheng
Zheng, Yan-Dan
Yuan, Yan
Chen, Shi-Chun
Xie, Bao-Cheng
author_facet Zhang, Yu-Sheng
Zheng, Yan-Dan
Yuan, Yan
Chen, Shi-Chun
Xie, Bao-Cheng
author_sort Zhang, Yu-Sheng
collection PubMed
description PURPOSE: Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium–glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS: One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58–13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04–0.93) and voglibose (RR 0.03; 0–0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32–2.1), follow-up duration (0.79; 0.27–1.64), and sex distribution (0.63; 0.15–1.56). CONCLUSIONS: We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. SYSTEMATIC REVIEW REGISTRATION: This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
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spelling pubmed-85532572021-10-29 Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis Zhang, Yu-Sheng Zheng, Yan-Dan Yuan, Yan Chen, Shi-Chun Xie, Bao-Cheng Front Endocrinol (Lausanne) Endocrinology PURPOSE: Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium–glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS: One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58–13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04–0.93) and voglibose (RR 0.03; 0–0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32–2.1), follow-up duration (0.79; 0.27–1.64), and sex distribution (0.63; 0.15–1.56). CONCLUSIONS: We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. SYSTEMATIC REVIEW REGISTRATION: This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464). Frontiers Media S.A. 2021-10-14 /pmc/articles/PMC8553257/ /pubmed/34721294 http://dx.doi.org/10.3389/fendo.2021.735824 Text en Copyright © 2021 Zhang, Zheng, Yuan, Chen and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Zhang, Yu-Sheng
Zheng, Yan-Dan
Yuan, Yan
Chen, Shi-Chun
Xie, Bao-Cheng
Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title_full Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title_fullStr Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title_full_unstemmed Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title_short Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis
title_sort effects of anti-diabetic drugs on fracture risk: a systematic review and network meta-analysis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553257/
https://www.ncbi.nlm.nih.gov/pubmed/34721294
http://dx.doi.org/10.3389/fendo.2021.735824
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