痛风和2型糖尿病患者启动钠葡萄糖共转运蛋白2抑制剂后痛风相关药物的使用：基于人群的靶向试验仿真研究

摘要(中文译文)

钠葡萄糖协同转运蛋白2抑制剂（SGLT2i）可降低血清尿酸水平，并与复发性痛风发作的风险较低有关。我们使用靶向试验模拟来比较痛风患者使用SGLT2i与二肽基肽酶4抑制剂（DPP-4is）（主要比较物）（主要对照物）的别嘌呤醇起始率和抗炎药（高剂量糖皮质激素、非甾体抗炎药[NSAID]、秋水仙素）和利尿剂（原型血清尿酸盐升高药物）的使用率，胰高血糖素样肽1受体激动剂（GLP-1RAs）作为替代比较物。从普通人群数据库中，我们确定了痛风和合并2型糖尿病的患者，并使用Cox比例风险和泊松回归以及治疗加权的逆概率来模拟随机分组到SGLT2i或DPP-4i/GLP-1RA。我们还在电子健康记录数据集中复制了这一分析，并进一步调整了血清尿酸和BMI。在26739名痛风和2型糖尿病患者（平均年龄66岁）中，67%患有多药治疗。SGLT2i引发剂的别嘌呤醇引发率低于DPP-4i，风险比为0.62（95%CI 0.52-0.73）。在基线时使用利尿剂的患者中，相关性更强（相互作用P=0.03），在将SGLT2i与GLP-1RA进行比较并在次要数据集中考虑血清尿酸盐和BMI时，相关性仍然存在。SGLT2i还与低剂量糖皮质激素、非甾体抗炎药、秋水仙碱和利尿剂的分配率相关，其比率分别为0.78（95%CI 0.74-0.83）、0.85（95%CI 0.80-0.92）、0.87（95%CI 0.83-0.92和0.87（95%CI 0.85-0.89）。对于痛风和2型糖尿病患者，SGLT2i可能会减少痛风相关药物的使用，这反过来又可能减少这一高危人群中非甾体抗炎药和糖皮质激素对心血管肾脏代谢的有害影响。

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) lower serum urate and are associated with a lower risk of recurrent gout flares. We used target trial emulation to compare rates of allopurinol initiation and use of anti-inflammatories (high-dose glucocorticoids, nonsteroidal anti-inflammatory drugs [NSAIDs], colchicine) and diuretics (prototypic serum urate-raising medication) among patients with gout using SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is) (primary comparator), with glucagon-like peptide 1 receptor agonists (GLP-1RAs) as an alternative comparator. From a general population database, we identified patients with gout and comorbid type 2 diabetes and used Cox proportional hazards and Poisson regressions with inverse probability of treatment weighting to emulate randomization to SGLT2i or DPP-4i/GLP-1RA. We also replicated the analysis in an electronic health record data set with further adjustment for serum urate and BMI. Among 26,739 adults with gout and type 2 diabetes (mean age 66 years), 67% had polypharmacy. Allopurinol initiation was lower among SGLT2i initiators than DPP-4i, with a hazard ratio of 0.62 (95% CI 0.52-0.73). Associations were stronger among those using diuretics at baseline (P for interaction = 0.03) and persisted when comparing SGLT2i with GLP-1RA and accounting for serum urate and BMI in the secondary data set. SGLT2i was also associated with lower rates of high-dose glucocorticoid, NSAID, colchicine, and diuretic dispensing, with rate ratios of 0.78 (95% CI 0.74-0.83), 0.85 (95% CI 0.80-0.92), 0.87 (95% CI 0.83-0.92), and 0.87 (95% CI 0.85-0.89), respectively. For patients with gout and type 2 diabetes, SGLT2is may reduce gout-related medication use, which could, in turn, reduce exposure to the harmful cardiovascular-kidney-metabolic effects of NSAIDs and glucocorticoids in this high-risk population.

如何引用