open access

Vol 72, No 4 (2021)
Original paper
Submitted: 2021-01-29
Accepted: 2021-03-15
Published online: 2021-03-31
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Evaluation of the risk of fracture in type 2 diabetes mellitus patients with incretins: an updated meta-analysis

Qing-xin Kong1, Qiao Ruan1, Cheng Fan1, Bi-Lin Liu1, Li-Ping Reng1, Weiping Xu2
·
Pubmed: 34010433
·
Endokrynol Pol 2021;72(4):319-328.
Affiliations
  1. Chongqing Chemical Industry Vocational College, Chongqing, China
  2. Hospital of the Southwest University of Political Science and Law, Chongqing, China

open access

Vol 72, No 4 (2021)
Original Paper
Submitted: 2021-01-29
Accepted: 2021-03-15
Published online: 2021-03-31

Abstract

Introduction: The effect of incretins including dipeptidyl peptidase 4 inhibitors (DPP4-Is) and glucagon-like peptide1 receptor agonists (GLP1-ras) in the treatment of type 2 diabetes increasing the risk of fracture remains controversial. No meta-analysis has been written to discuss this from the prospective interventional studies.

The objective was to evaluate the association between the use of incretins and fracture risk.

Material and methods: Multiple databases were searched for original articles that investigated the relationship between the use of incretin agents and fracture risk, up to December 2019. Trials using the Mantel-Haenszel method to calculate OR and 95% CI were pooled. The multiple sensitivity, heterogeneity, publication bias, and quality were analysed among the studies to evaluate the robustness of results.

Results: The fixed-effects model was used on account of the I2 test for heterogeneity (I2 = 0.0%). Incretins were not associated with fracture risk [0.97 (95% CI: 0.88–1.08)]. But in the subgroup analysis, when sitagliptin 100 mg per day (OR 0.495, 95% CI: 0.304–0.806) or liraglutide 1.8 mg per day was administered (OR 0.621, 95% CI: 0.413–0.933), it reduced fracture risk. The sensitivity analysis and publication bias prompted the robustness of results.

Conclusions: This meta-analysis suggested that the current use of incretins not only is safe for fracture in type 2 diabetes patients from RCT studies, but also, when sitagliptin 100 mg or liraglutide 1.8 mg per day was administered, it may exhibit protective effects on bone metabolism.

 

Abstract

Introduction: The effect of incretins including dipeptidyl peptidase 4 inhibitors (DPP4-Is) and glucagon-like peptide1 receptor agonists (GLP1-ras) in the treatment of type 2 diabetes increasing the risk of fracture remains controversial. No meta-analysis has been written to discuss this from the prospective interventional studies.

The objective was to evaluate the association between the use of incretins and fracture risk.

Material and methods: Multiple databases were searched for original articles that investigated the relationship between the use of incretin agents and fracture risk, up to December 2019. Trials using the Mantel-Haenszel method to calculate OR and 95% CI were pooled. The multiple sensitivity, heterogeneity, publication bias, and quality were analysed among the studies to evaluate the robustness of results.

Results: The fixed-effects model was used on account of the I2 test for heterogeneity (I2 = 0.0%). Incretins were not associated with fracture risk [0.97 (95% CI: 0.88–1.08)]. But in the subgroup analysis, when sitagliptin 100 mg per day (OR 0.495, 95% CI: 0.304–0.806) or liraglutide 1.8 mg per day was administered (OR 0.621, 95% CI: 0.413–0.933), it reduced fracture risk. The sensitivity analysis and publication bias prompted the robustness of results.

Conclusions: This meta-analysis suggested that the current use of incretins not only is safe for fracture in type 2 diabetes patients from RCT studies, but also, when sitagliptin 100 mg or liraglutide 1.8 mg per day was administered, it may exhibit protective effects on bone metabolism.

 

Get Citation

Keywords

incretins; GLP-1; DPP-4; fracture; meta-analysis; RCT

About this article
Title

Evaluation of the risk of fracture in type 2 diabetes mellitus patients with incretins: an updated meta-analysis

Journal

Endokrynologia Polska

Issue

Vol 72, No 4 (2021)

Article type

Original paper

Pages

319-328

Published online

2021-03-31

Page views

1360

Article views/downloads

768

DOI

10.5603/EP.a2021.0031

Pubmed

34010433

Bibliographic record

Endokrynol Pol 2021;72(4):319-328.

Keywords

incretins
GLP-1
DPP-4
fracture
meta-analysis
RCT

Authors

Qing-xin Kong
Qiao Ruan
Cheng Fan
Bi-Lin Liu
Li-Ping Reng
Weiping Xu

References (33)
  1. Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc. 2003; 51(3): 364–370.
  2. Moayeri A, Mohamadpour M, Mousavi SF, et al. Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Ther Clin Risk Manag. 2017; 13: 455–468.
  3. Wolverton D, Blair MM. Fracture risk associated with common medications used in treating type 2 diabetes mellitus. Am J Health Syst Pharm. 2017; 74(15): 1143–1151.
  4. Schwartz AV, Lecka-Czernik B. Diabetes, bone and glucose-lowering agents: basic biology. Diabetologia. 2017; 60(7): 1163–1169.
  5. Schwartz AV, Lecka-Czernik B. Diabetes, bone and glucose-lowering agents: basic biology. Diabetologia. 2017; 60(7): 1163–1169.
  6. Schott G, Martinez YV, Ediriweera de Silva RE, et al. Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing. BMC Geriatr. 2017; 17(Suppl 1): 226.
  7. Tasyurek HM, Altunbas HA, Balci MK, et al. Incretins: their physiology and application in the treatment of diabetes mellitus. Diabetes Metab Res Rev. 2014; 30(5): 354–371.
  8. Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018; 20 Suppl 1: 5–21.
  9. Monami M, Dicembrini I, Antenore A, et al. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 2011; 34(11): 2474–2476.
  10. Mabilleau G, Mieczkowska A, Chappard D. Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials. J Diabetes. 2014; 6(3): 260–266.
  11. Su B, Sheng H, Zhang M, et al. Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists' treatment: a meta-analysis of randomized controlled trials. Endocrine. 2015; 48(1): 107–115.
  12. Fu J, Zhu J, Hao Y, et al. Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials. Sci Rep. 2016; 6: 29104.
  13. Dombrowski S, Kostev K, Jacob L. Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany-A retrospective analysis of real-world data. Osteoporos Int. 2017; 28(8): 2421–2428.
  14. Yang J, Huang C, Wu S, et al. The effects of dipeptidyl peptidase-4 inhibitors on bone fracture among patients with type 2 diabetes mellitus: A network meta-analysis of randomized controlled trials. PLoS One. 2017; 12(12): e0187537.
  15. Driessen JHM, de Vries F, van Onzenoort H, et al. The use of incretins and fractures — a meta-analysis on population-based real life data. Br J Clin Pharmacol. 2017; 83(4): 923–926.
  16. Knobloch K, Yoon U, Vogt PM. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias. J Craniomaxillofac Surg. 2011; 39(2): 91–92.
  17. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557–560.
  18. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 17(1): 1–12.
  19. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019; 10: ED000142.
  20. Begg C, Mazumdar M. Operating Characteristics of a Rank Correlation Test for Publication Bias. Biometrics. 1994; 50(4): 1088.
  21. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629–634.
  22. Gilbert MP, Marre M, Holst JJ, et al. Comparison of the Long-Term Effects of Liraglutide and Glimepiride Monotherapy on Bone Mineral Density in Patients with Type 2 Diabetes. Endocr Pract. 2016; 22(4): 406–411.
  23. Wen B, Zhao Lu, Zhao H, et al. Liraglutide exerts a bone-protective effect in ovariectomized rats with streptozotocin-induced diabetes by inhibiting osteoclastogenesis. Exp Ther Med. 2018; 15(6): 5077–5083.
  24. Mabilleau G, Pereira M, Chenu C. Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists. J Endocrinol. 2018; 236(1): R29–R42.
  25. Zhang L, Yang M, Ren H, et al. GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. Liver Int. 2013; 33(5): 794–804.
  26. Vilsboll T. Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc). 2009; 45(2): 101–113.
  27. Cusick T, Mu J, Pennypacker BL, et al. Bone loss in the oestrogen-depleted rat is not exacerbated by sitagliptin, either alone or in combination with a thiazolidinedione. Diabetes Obes Metab. 2013; 15(10): 954–957.
  28. Hegazy SK. Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmenopausal diabetic women. J Bone Miner Metab. 2015; 33(2): 207–212.
  29. Mabilleau G, Mieczkowska A, Irwin N, et al. Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor. J Endocrinol. 2013; 219(1): 59–68.
  30. Montagnani A, Gonnelli S, Alessandri M, et al. Osteoporosis and risk of fracture in patients with diabetes: an update. Aging Clin Exp Res. 2011; 23(2): 84–90.
  31. Mabilleau G, Gobron B, Bouvard B, et al. Incretin-based therapy for the treatment of bone fragility in diabetes mellitus. Peptides. 2018; 100: 108–113.
  32. Scheen AJ. The safety of gliptins : updated data in 2018. Expert Opin Drug Saf. 2018; 17(4): 387–405.
  33. Josse RG, Majumdar SR, Zheng Y, et al. TECOS Study Group. Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS trial. Diabetes Obes Metab. 2017; 19(1): 78–86.

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