Diabetes & Endocrinology Research and Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK.
Centre for Epidemiology Versus Arthritis, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Diabetologia. 2023 Oct;66(10):1869-1881. doi: 10.1007/s00125-023-05975-8. Epub 2023 Jul 28.
AIMS/HYPOTHESIS: Insulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.
We performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.
We identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA (-2.6 mmol/mol [-0.2%] with SGLT2i and -5.4 mmol/mol [-0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m vs -7.2 ml/min per 1.73 m, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.
CONCLUSIONS/INTERPRETATION: Both SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.
目的/假设：胰岛素是 1 型糖尿病的主要治疗方法。然而，辅助使用了其他降血糖疗法，但在 1 型糖尿病中重要的是标签外用药。以前很少有工作评估这些疗法的长期疗效和心肾获益的安全性。我们旨在研究钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）和胰高血糖素样肽-1 受体激动剂（GLP-1RA）在 1 型糖尿病患者中的实际影响，以评估对血糖水平、不良事件和心肾结局的影响。
我们对 TriNetX 平台上所有年龄在 18 岁或以上的 1 型糖尿病患者进行了回顾性队列研究，TriNetX 是一个提供实时匿名医疗记录的全球合作网络。我们纳入了至少接受 SGLT2i 或 GLP-1RA 治疗 6 个月的患者，并分析了治疗开始后 5 年的疗效、安全性和心肾结局。
我们确定了 196691 名 1 型糖尿病患者，其中 13%的患者在胰岛素治疗的基础上加用辅助降血糖药物。核心分析包括 1822 名接受 GLP-1RA 治疗的患者和 992 名接受 SGLT2i 治疗的患者。两种药物均显著降低 HbA1c（SGLT2i 组为-2.6mmol/mol[-0.2%]，GLP-1RA 组为-5.4mmol/mol[-0.5%]）。与 GLP-1RA 治疗组相比，SGLT2i 治疗组在 5 年内 eGFR 得到了维持（分别为+3.5ml/min/1.73m2 和-7.2ml/min/1.73m2，包括有慢性肾脏病（CKD）的患者）。SGLT2i 治疗组发生糖尿病酮症酸中毒（DKA）的比例更高（RR 2.08[95%CI 1.05,4.12]p=0.0309）和尿路感染/肾盂肾炎（RR 2.27[95%CI 1.12,4.55]p=0.019），而 GLP-1RA 治疗组则更低。然而，与 GLP-1RA 治疗组相比，SGLT2i 治疗组更不容易发生心力衰竭（RR 0.44[95%CI 0.23,0.83]p=0.0092）、CKD（RR 0.49[95%CI 0.28,0.86]p=0.0118）和因任何原因住院（RR 0.59[95%CI 0.46,0.76]p≤0.0001）。
结论/解释：SGLT2i 和 GLP-1RA 作为 1 型糖尿病的辅助治疗药物都具有潜在的益处。SGLT2i 具有心肾获益，但与 GLP-1RA 治疗相比，DKA 和尿路感染的风险增加。需要长期评估这些辅助治疗的疗效和安全性，以指导其在 1 型糖尿病患者中的应用。
