Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Pharmacoepidemiol Drug Saf. 2022 May;31(5):566-576. doi: 10.1002/pds.5406. Epub 2022 Jan 17.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-line monotherapy.
Using claims data from two US commercial health insurance and Medicare, we identified patients with T2D aged ≥18 years (>65 years in Medicare) initiating first-line SGLT-2i or metformin from 2013 through 2019. Standardized differences (SDs) for patient characteristics were assessed during four consecutive calendar time blocks (T1:4/2013-12/2014; T2:1/2015-6/2016; T3:7/2016-12/2017; and T4:1/2018-12/2019). We also estimated the propensity score of receiving SGLT-2i versus metformin within each time block and evaluated time trends in model discrimination with c-statistics.
We identified 9113 initiators of first-line SGLT-2i and 810 348 initiators of first-line metformin. During T1, SGLT-2i initiators were younger (SD = -0.24) and less likely to have seen cardiologists (-0.07) with a similar prevalence of CVD (0.04) compared with metformin. During T4, patients were more balanced for age (-0.01). Cardiologist visits (0.08) and CVD (0.25) became more prevalent among SGLT-2i initiators.
When comparing initiators of first-line SGLT-2i versus metformin, imbalances in patient characteristics evolved from 2013 through 2019, particularly channeling SGLT-2i to individuals at high cardiovascular risk. Evolving channeling in prescribing first-line SGLT-2i should be expected and accounted for in non-randomized comparative effectiveness research.
钠-葡萄糖协同转运蛋白 2 抑制剂(SGLT-2i)正日益被视为 2 型糖尿病(T2D)的一线治疗药物。SGLT-2i 在心血管结局试验中的获益可能导致将 SGLT-2i 优先用于高心血管风险患者,这可能导致非随机研究中 SGLT-2i 作为一线治疗药物的混杂。我们评估了起始 SGLT-2i 与二甲双胍作为一线单药治疗的患者特征的演变性不平衡。
我们使用来自美国两家商业健康保险和医疗保险的索赔数据,确定了 2013 年至 2019 年期间起始一线 SGLT-2i 或二甲双胍治疗的年龄≥18 岁(医疗保险中>65 岁)的 T2D 患者。在四个连续的日历时间块(T1:2013 年 4 月至 2014 年 12 月;T2:2015 年 1 月至 2016 年 6 月;T3:2016 年 7 月至 2017 年 12 月;T4:2018 年 1 月至 2019 年 12 月)评估患者特征的标准化差异(SD)。我们还在每个时间块内估计了接受 SGLT-2i 与二甲双胍的倾向评分,并使用 C 统计量评估模型判别力的时间趋势。
我们确定了 9113 名起始一线 SGLT-2i 患者和 810348 名起始一线二甲双胍患者。在 T1 期间,与二甲双胍相比,SGLT-2i 起始者年龄较小(SD=-0.24),看心脏病专家的可能性较小(-0.07),CVD 的流行率相似(0.04)。在 T4 期间,年龄的患者更为均衡(-0.01)。心脏病专家就诊(0.08)和 CVD(0.25)在 SGLT-2i 起始者中更为常见。
在比较起始一线 SGLT-2i 与二甲双胍的患者时,2013 年至 2019 年期间患者特征的不平衡有所演变,特别是将 SGLT-2i 用于高心血管风险个体。在非随机比较疗效研究中,应预期并考虑到一线 SGLT-2i 处方的演变性引导。