External control arm with real world data to assess the effect of semaglutide on chronic kidney disease risk among patients with type 2 diabetes

Clinical trials have shown semaglutide effective in mitigating risks associated with type 2 diabetes and chronic kidney disease. However, semaglutide’s real-world effectiveness and long-term outcomes are not fully established. Using 2019–2024 Kythera Labs data, an external control arm was created using criteria identified in the FLOW clinical trial. Primary outcomes were major kidney disease events (kidney failure onset and ≥ 50% reduction in estimated glomerular filtration rate from baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes. The control arm (n = 896,257) was compared with the clinical trial cohort (n = 1,766). After propensity score matching on age, sex, socioeconomic status, and comorbidities, semaglutide treatment was associated with a 26% reduction in primary event risk compared with the comparator group (702 vs 1,068 events; HR: 0.74; 95% CI, 0.67–0.81), consistent with the 24% risk reduction observed in the clinical trial. Semaglutide treatment was linked to a significantly lower risk of clinically relevant renal outcomes. Our findings provide robust real-world evidence that supports the FLOW trial results regarding the renoprotective effects of semaglutide, highlighting its promise as an effective therapeutic option for managing renal complications.临床研究已证实，司美格鲁肽（semaglutide）可有效降低2型糖尿病与慢性肾脏病相关的疾病风险。但目前司美格鲁肽的真实世界有效性及长期临床结局尚未完全明确。本研究利用2019–2024年基瑟拉实验室（Kythera Labs）的数据，参照FLOW临床试验确定的标准构建了外部对照队列。本研究的主要结局指标为主要肾脏不良事件，包括肾衰竭发作及估算肾小球滤过率（estimated glomerular filtration rate）较基线水平降低≥50%。本研究采用倾向得分匹配（propensity score matching）与Cox回归（Cox regression）分析，以确定校正风险后的临床结局。将外部对照队列（n=896257）与临床试验队列（n=1766）进行对比后，在对年龄、性别、社会经济地位及合并症开展倾向得分匹配后发现，相较于对照队列，司美格鲁肽治疗组的主要事件发生风险降低26%（事件数分别为702例与1068例；风险比HR=0.74；95%置信区间CI：0.67–0.81），这与临床试验中观察到的24%风险降低结果相符。司美格鲁肽治疗可显著降低临床相关性肾脏结局的发生风险。本研究结果提供了强有力的真实世界证据，支持FLOW临床试验关于司美格鲁肽肾脏保护作用的结论，凸显其作为肾脏并发症管理有效治疗方案的应用前景。