Feher Michael, Hinton William, Forbes Anna, Munro Neil, Joy Mark, Wheeler David, de Lusignan Simon
Clinical Informatics and Health Outcomes Research Group, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Clinical Informatics, University of Surrey, Guildford, United Kingdom.
JMIR Res Protoc. 2022 Jul 19;11(7):e34206. doi: 10.2196/34206.
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are both considered to be part of standard care in the management of glycemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary kidney end points for individual drugs within each medication class. Despite the potential benefits of combining SGLT2is and GLP-1RAs for glycemia management, according to national and international guideline recommendations, there is currently limited data on kidney end points for this drug combination.
The aims of the study are to assess the real-world effects of combination SGLT2i and GLP-1RA therapies for diabetes management on kidney end points, glycemic control, and weight in people with type 2 diabetes who are being treated with renin-angiotensin system blockade medication.
This retrospective cohort study will use the electronic health records of people with type 2 diabetes that are registered with general practices covering over 15 million people in England and Wales and are included in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network. A propensity score-matched cohort of prevalent new users of SGLT2is and GLP-1RAs and those who have been prescribed SGLT2is and GLP-1RAs in combination will be identified. They will be matched based on drug histories, comorbidities, and demographics. A repeated-measures, multilevel, linear regression analysis will be performed to compare the mean change (from baseline) in estimated glomerular filtration rate at 12 and 24 months between those who switched to combined therapy and those continuing monotherapy with an SGLT2i or GLP-1RA. The secondary end points will be albuminuria, serum creatinine level, glycated hemoglobin level, and BMI. These will also be assessed for change at the 12- and 24-month follow-ups.
The study is due to commence in March 2022 and is expected to be complete by September 2022.
Our study will be the first to assess the impact of combination SGLT2i and GLP-1RA therapy in type 2 diabetes on primary kidney end points from a real-world perspective.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34206.
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）均被视为2型糖尿病血糖管理标准治疗的一部分。近期试验证据表明，每类药物中的个别药物对原发性肾脏终点有益。尽管联合使用SGLT2i和GLP-1RA进行血糖管理有潜在益处，但根据国家和国际指南建议，目前关于这种药物联合治疗的肾脏终点数据有限。
本研究旨在评估联合使用SGLT2i和GLP-1RA疗法治疗糖尿病对接受肾素-血管紧张素系统阻断药物治疗的2型糖尿病患者的肾脏终点、血糖控制和体重的实际影响。
这项回顾性队列研究将使用2型糖尿病患者的电子健康记录，这些记录来自覆盖英格兰和威尔士1500多万人的全科医疗注册信息，并纳入牛津-皇家全科医师学院研究与监测中心网络。将确定一个倾向评分匹配队列，其中包括SGLT2i和GLP-1RA的新使用者以及联合使用SGLT2i和GLP-1RA的患者。将根据用药史、合并症和人口统计学特征进行匹配。将进行重复测量、多级线性回归分析，以比较改用联合治疗的患者与继续使用SGLT2i或GLP-1RA单一疗法的患者在12个月和24个月时估计肾小球滤过率的平均变化（相对于基线）。次要终点将是蛋白尿、血清肌酐水平、糖化血红蛋白水平和体重指数。这些指标也将在12个月和24个月的随访中评估变化情况。
该研究将于2022年3月开始，预计2022年9月完成。
我们的研究将首次从实际应用角度评估联合使用SGLT2i和GLP-1RA疗法对2型糖尿病原发性肾脏终点的影响。
国际注册报告识别码（IRRID）：PRR1-10.2196/34206
