钠-葡萄糖共转运蛋白受体选择性对钠-葡萄糖共转运蛋白2抑制剂引起2型糖尿病患者骨折的影响:系统综述与网状Meta分析

Effect of different sodium-glucose co-transporter receptor-selective sodium-glucose cotransporter 2 inhibitors on the risk of fracture in type 2 diabetes patients:a systematic review and network meta-analysis

目的系统评价受体选择性对钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)引起2型糖尿病(T2DM)患者发生骨折风险的影响。方法检索美国国立医学图书馆数据库(PubMed)、医学文摘数据库(EMbase)、Clinical trials和Cochrane循证医学数据库(Cochrane Library)中自建库以来至2023年6月30日收录的涉及T2DM患者使用SGLT2i类药物,且报告了骨折结局的所有随机对照试验。经过筛选后提取纳入文献的相关信息,对纳入文献进行传统Meta分析,随后将涉及的SGLT2i类药物按其对受体的位点选择性分为高选择性[药物对于钠-葡萄糖共转运蛋白(SGLT)1/2位点IC50的比值≥900]和低选择性(药物对于SGLT 1/2位点IC50的比值<900)两组,并将对照分为其他降糖药组和安慰剂组,以上4组进行网状Meta分析。结果最终纳入44篇文献,总样本量为52276例。传统Meta分析结果显示,非SGLT2i干预措施与SGLT2i类药物引起T2DM患者骨折的风险差异无统计学意义(OR=1.07,95%CI 0.88~1.30)。网状Meta结果显示,与安慰剂相比,高选择性SGLT2i(OR=0.94,95%CI 0.64~1.38)和低选择性SGLT2i(OR=1.19,95%CI 0.76~1.88)T2DM患者的骨折发生风险差异均无统计学意义,且高选择性SGLT2i和低选择性SGLT2i相比骨折风险差异也无统计学意义(OR=0.79,95%CI 0.44~1.40)。结论T2DM患者使用SGLT2i类药物并未发现骨折风险增加,且SGLT2i类药物的骨折风险不受该类药物受体位点选择性差异的影响。

Objective To systematically review the risk of fracture in type 2 diabetes mellitus(T2DM)patients induced by different receptor-selective sodium-glucose co-transporter 2 inhibitors(SGLT2i).Methods A systematic search of the National Library of Medicine database(PubMed),the Embase database,Clinical trials,and the Cochrane Library was conducted from the inception of each database until June 30,2023 to identify all randomized controlled trials in T2DM patients using SGLT2i drugs that reported fracture outcomes.After a selection process,data were extracted from the trials.A traditional meta-analysis was performed based on the data.Subsequently,the included trials were categorized into two groups based on the selectivity of the drugs for their receptor sites:high selectivity[the drug has an IC50 ratio of≥900 at the sodium-glucose cotransporter(SGLT)1/2 site]and low selectivity[the drug has an IC50 ratio of<900 at the SGLT 1/2 site].Control groups were further categorized into other anti-hyperglycemic medications and placebo.A network meta-analysis was performed with these four groups.Results A total of 44 trials were included in this study,with a total sample size of 52276 cases.The results of traditional meta-analysis showed that there was no statistically significant difference in the risk of fracture in T2DM patients caused by SGLT2i drugs compared with non-SGLT2i interventions(OR=1.07,95%CI 0.88-1.30).The network meta-analysis results indicated that compared with placebo,neither high-selectivity SGLT2i(OR=0.94,95%CI 0.64-1.38)nor low-selectivity SGLT2i(OR=1.19,95%CI 0.76-1.88)showed a statistically significant difference in the risk of fracture in T2DM patients,and there was no statistically significant difference in the risk of fracture between the high-selectivity and low-selectivity SGLT2i groups(OR=0.79,95%CI 0.44-1.40).Conclusion The use of SGLT2i drugs in T2DM patients does not increase the risk of fracture,and the fracture risk associated with SGLT2i drugs is not influenced by the differences in the receptor site selectivity of these drugs.