Abstract：
OBJECTIVE: This study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data.
METHODS: We conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation.
RESULTS: Prior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74-0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001).
CONCLUSIONS: In this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.
METHODS: We conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation.
RESULTS: Prior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74-0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001).
CONCLUSIONS: In this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.
摘要：
目的：本研究旨在使用真实世界数据评估钠-葡萄糖协同转运蛋白-2抑制剂（SGLT2i）和胰高血糖素样肽-1受体激动剂（GLP-1Ra）与2型糖尿病（T2D）患者痛风发生率的相对相关性。
方法：我们使用来自TriNetX（国际联合数据库）的数据进行了一项队列研究。我们纳入了开始服用二甲双胍或胰岛素的患者，单独或与SGLT2i或GLP-1Ra一起使用，在分析日期前至少2年。我们对26个相关特征的倾向评分匹配(PSM)(1:1)。进行事件发生时间分析以评估痛风的发生率，全因死亡率（阳性对照），和带状疱疹感染（阴性对照）在药物开始后5年。
结果：在PSM之前，队列编号如下：二甲双胍对照，1,111,449；SGLT2i与二甲双胍，101,706;GLP-1Ra与二甲双胍,110,180，胰岛素控制，1,398,066;SGLT2i与胰岛素，68,697;和GLP-1Ra与胰岛素，99,693。与二甲双胍对照队列相比，SGLT2i与二甲双胍一起显示5年时痛风发生率显著降低(HR0.75[95%CI0.69-0.82]，P<0.0001)。同样，与胰岛素对照组相比，SGLT2i与胰岛素对照组相比，5年时痛风发生率显着降低（HR0.83[95％CI0.74-0.92]，P<0.0001)。相反，在使用GLP-1Ra和匹配的对照之间,痛风发生率没有显著差异.亚组分析显示，与GLP-1Ra相比，使用SGLT2i的痛风发生率降低，在使用二甲双胍的组中(HR0.77[95%CI0.70-0.86]，P<0.0001)或胰岛素(HR0.82[95%CI0.73-0.91)]，P<0.0001)。
结论：在这项大规模的现实世界研究中，与胰岛素和二甲双胍对照相比，T2D患者使用SGLT2i与痛风发生率较低相关。这些发现表明SGLT2i作为治疗该人群痛风的有希望的治疗选择的潜力。
方法：我们使用来自TriNetX（国际联合数据库）的数据进行了一项队列研究。我们纳入了开始服用二甲双胍或胰岛素的患者，单独或与SGLT2i或GLP-1Ra一起使用，在分析日期前至少2年。我们对26个相关特征的倾向评分匹配(PSM)(1:1)。进行事件发生时间分析以评估痛风的发生率，全因死亡率（阳性对照），和带状疱疹感染（阴性对照）在药物开始后5年。
结果：在PSM之前，队列编号如下：二甲双胍对照，1,111,449；SGLT2i与二甲双胍，101,706;GLP-1Ra与二甲双胍,110,180，胰岛素控制，1,398,066;SGLT2i与胰岛素，68,697;和GLP-1Ra与胰岛素，99,693。与二甲双胍对照队列相比，SGLT2i与二甲双胍一起显示5年时痛风发生率显著降低(HR0.75[95%CI0.69-0.82]，P<0.0001)。同样，与胰岛素对照组相比，SGLT2i与胰岛素对照组相比，5年时痛风发生率显着降低（HR0.83[95％CI0.74-0.92]，P<0.0001)。相反，在使用GLP-1Ra和匹配的对照之间,痛风发生率没有显著差异.亚组分析显示，与GLP-1Ra相比，使用SGLT2i的痛风发生率降低，在使用二甲双胍的组中(HR0.77[95%CI0.70-0.86]，P<0.0001)或胰岛素(HR0.82[95%CI0.73-0.91)]，P<0.0001)。
结论：在这项大规模的现实世界研究中，与胰岛素和二甲双胍对照相比，T2D患者使用SGLT2i与痛风发生率较低相关。这些发现表明SGLT2i作为治疗该人群痛风的有希望的治疗选择的潜力。
