Driessen Johanna H M, Henry Ronald M A, van Onzenoort Hein A W, Lalmohamed Arief, Burden Andrea M, Prieto-Alhambra Daniel, Neef Cees, Leufkens Hubert G M, de Vries Frank
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Calcif Tissue Int. 2015 Aug;97(2):104-12. doi: 10.1007/s00223-015-9993-5. Epub 2015 Apr 17.
Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007-2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82-1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72-1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.
胰高血糖素样肽-1受体激动剂（GLP1-ra）是一类相对较新的抗高血糖药物，可能对骨代谢产生积极影响，从而降低（骨质疏松性）骨折风险。关于GLP1-ra对骨折风险影响的数据稀缺，且仅限于临床试验数据。本研究的目的是在一个基于人群的队列中，调查GLP1-ra的使用与骨折风险之间的关联。我们利用临床实践研究数据链（CPRD）数据库（2007 - 2012年）的数据进行了一项基于人群的队列研究。研究人群（N = 216,816）包括所有患有2型糖尿病且至少有一张非胰岛素抗糖尿病药物处方且年龄超过18岁的个体。使用Cox比例风险模型来估计GLP1-ra使用者与从未使用过GLP1-ra使用者骨折的风险比。对年龄、性别、生活方式、合并症和其他药物的使用进行了时间依赖性调整。与从未使用GLP1-ra相比，当前使用GLP1-ra并没有降低骨折风险（调整后的风险比为0.99，95%置信区间为0.82 - 1.19）。当前使用GLP1-ra也没有降低骨质疏松性骨折风险（调整后的风险比为0.97；95%置信区间为0.72 - 1.32）。此外，根据累积剂量分层并未显示随着GLP1-ra累积剂量增加骨折风险降低。我们在一项基于人群的队列研究中表明，与其他抗高血糖药物使用者相比，使用GLP1-ra与降低骨折风险无关。需要进一步的研究来阐明GLP1-ra对骨骼的潜在作用机制。
