中南大学湘雅医院雷光华教授团队研究了地诺单抗与成人骨质疏松患者2型糖尿病发病率的关系。2023年4月18日出版的《英国医学杂志》发表了这项成果。

为了比较地诺单抗与口服双膦酸盐在降低成人骨质疏松症患者患2型糖尿病风险方面的作用，研究组进行了一项基于人群的研究，包括使用电子健康记录模拟随机目标试验。使用1995-2021年英国IQVIA医疗研究数据初级保健数据库。招募45岁及以上的成年人，使用地诺单抗或口服双膦酸盐治疗骨质疏松症。根据诊断代码的定义，主要结局为发生2型糖尿病。Cox比例风险模型用于估计校正后的风险比和95%置信区间，并使用治疗后的方法将地诺单抗与口服双膦酸盐进行比较。

4301名新的地诺单抗使用者与21038名口服双磷酸盐使用者的倾向评分相匹配，平均随访2.2年。地诺单抗使用者的2型糖尿病发病率为每1000人-年5.7例，口服双磷酸盐使用者为每1000人-年8.3例。使用地诺单抗可降低患2型糖尿病的风险（风险比为0.68）。与口服双膦酸盐相比，糖尿病前期患者似乎从地诺单抗中获益更多（风险比为0.54），对于体重指数≥30（0.65）的患者也是如此。

综上，在这项基于人群的研究中，在患有骨质疏松症的成年人中，与口服双膦酸盐相比，使用地诺单抗可降低2型糖尿病的发病风险。这项研究在人群水平上提供了证据，表明与口服双膦酸盐相比，地诺单抗可能对葡萄糖代谢有额外的益处。

附：英文原文

Title: Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Author: Houchen Lyu, Sizheng Steven Zhao, Licheng Zhang, Jie Wei, Xiaoxiao Li, Hui Li, Yi Liu, Pengbin Yin, Vibeke Norvang, Kazuki Yoshida, Sara K Tedeschi, Chao Zeng, Guanghua Lei, Peifu Tang, Daniel H Solomon

Issue&Volume: 2023/04/18

Abstract:

Objective To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.

Design Population based study involving emulation of a randomized target trial using electronic health records.

Setting IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021.

Participants Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis.

Main outcome measures The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach.

Results 4301 new users of denosumab were matched on propensity score to 21038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06).

Conclusions In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.

DOI: 10.1136/bmj-2022-073435

Source: https://www.bmj.com/content/381/bmj-2022-073435