钠-葡萄糖协同转运蛋白-2抑制剂(SGLT2i)已证明对2型糖尿病(T2D)患者的心血管益处。这项自我对照病例系列研究旨在评估二甲双胍使用和SGLT2i相关红细胞增多症是否会影响其心血管益处。
从香港人群中发现了2015年至2020年间使用二甲双胍和/或SGLT2i处方的T2D患者。研究结果是复合心血管疾病(CVD),冠心病,因心力衰竭(HHF)住院,中风,和红细胞增多症。危险期是患者-时间,分为四个互斥窗口:(i)不使用SGLT2i的二甲双胍的“基线期”;(ii)SGLT2i前期;(iii)不使用二甲双胍的SGLT2i暴露;(iv)药物组合暴露。另一个SCCS模型用于评估红细胞增多症与SGLT2i暴露相关的心血管结局之间的关联。四个相互排斥的危险期包括(i)SGLT2i接触红细胞增多;(ii)SGLT2i接触无红细胞增多;(iii)SGLT2i接触无红细胞增多;(iv)SGLT2i接触无红细胞增多。采用条件泊松回归模型估计不同危险期事件的发生率比(IRR)。
在20,861名使用二甲双胍和/或SGLT2i处方的患者中,2575和1700例患者发生复合CVD和红细胞增多症,分别。与不使用SGLT2i的二甲双胍相比,SGLT2i的启动与复合CVD的较低风险相关,CHD,和HHF-无论是否存在(CVD:IRR=0.43,95%CI0.37-0.51;CHD:IRR=0.44,95%CI0.37-0.53;HHF:IRR=0.29,95%CI0.22-0.40;所有p<0.001)和没有伴随的二甲双胍(CVD:IRR=0.31,95%IRR=0.25-0.48CHD:95%LTCI=与二甲双胍-SGLT2i组合相比,单独暴露于SGLT2i与所有心血管结局的风险相当(均p>0.05).基线时红细胞增多症的发生率,SGLT2i不使用和使用二甲双胍的时间分别为每100人年0.75、3.06和3.27,分别。发生红细胞增多症的SGLT2i使用者患HHF的风险较未发生者低(IRR=0.38,95%CI0.14-0.99,p=0.049)。
我们的实际数据表明,使用二甲双胍并未减弱SGLT2i相关的心血管益处。进一步的研究将描述红细胞增多症作为SGLT2i相关心血管益处的替代标志物在减少HHF中的作用。
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have proven cardiovascular benefits in patients with type 2 diabetes (T2D). This self-controlled case series study aims to evaluate whether metformin use and SGLT2i-associated erythrocytosis influence its cardiovascular benefits.
T2D patients with metformin and/or SGLT2i prescriptions between 2015 and 2020 were identified from the Hong Kong population. Study outcomes were composite cardiovascular diseases (CVD), coronary heart disease (CHD), hospitalisation for heart failure (HHF), stroke, and erythrocytosis. Risk periods were patient-time divided into four mutually exclusive windows: (i) \'baseline period\' of metformin use without SGLT2i; (ii) pre-SGLT2i period; (iii) exposure to SGLT2i without metformin; and (iv) exposure to the drug combination. Another SCCS model was applied to evaluate the association between
erythrocytosis and cardiovascular outcomes regarding SGLT2i exposure. Four mutually exclusive risk periods included (i) SGLT2i exposure with erythrocytosis; (ii) SGLT2i exposure without
erythrocytosis; (iii) absence of SGLT2i exposure with
erythrocytosis; and (iv) absence of SGLT2i exposure without
erythrocytosis. Incidence rate ratios (IRR) of events at different risk periods were estimated using conditional Poisson regression model.
Among 20,861 patients with metformin and/or SGLT2i prescriptions, 2575 and 1700 patients with events of composite CVD and erythrocytosis were identified, respectively. Compared to metformin use without SGLT2i, SGLT2i initiation was associated with lower risks of composite CVD, CHD, and HHF-regardless of the presence (CVD: IRR = 0.43, 95% CI 0.37-0.51; CHD: IRR = 0.44, 95% CI 0.37-0.53; HHF: IRR = 0.29, 95% CI 0.22-0.40; all p < 0.001) and absence of concomitant metformin (CVD: IRR = 0.31, 95% CI 0.20-0.48; CHD: IRR = 0.38, 95% CI 0.25-0.59; HHF: IRR = 0.17, 95% CI 0.09-0.31; all p < 0.001); while SGLT2i was neutral on stroke risk. Compared to metformin-SGLT2i combination, exposure to SGLT2i alone was associated with comparable risks of all cardiovascular outcomes (all p > 0.05). Incidence rates of
erythrocytosis at baseline, SGLT2i without and with metformin use periods were 0.75, 3.06 and 3.27 per 100 person-years, respectively. SGLT2i users who developed erythrocytosis had lower risk of HHF (IRR = 0.38, 95% CI 0.14-0.99, p = 0.049) than those who did not.
Our real-world data suggested that SGLT2i-associated cardiovascular benefits were not attenuated by metformin use. Further studies will delineate the role of
erythrocytosis as a surrogate marker of SGLT2i-associated cardiovascular benefit in reducing HHF.