SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence

Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and is associated with poor clinical outcomes, including an increased risk of all-cause and cardiovascular mortality, as well as adverse economic and social effects. Slowing the development and progression of CKD remains an unmet clinical need in patients with T2DM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used for the management of T2DM and have effects beyond glucose lowering that include cardiovascular benefits and potential renoprotective effects. Although the glucose-lowering efficacy of these agents is dependent on renal function, the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m2. Clinical evidence has indicated that these agents can reduce the risk of development or worsening of albuminuria, a marker of renal damage, through a range of mechanisms. These include blood pressure lowering, reduction of intraglomerular pressure and hyperfiltration, modification of inflammatory processes, reduction of ischemia-related renal injury, and increases in glucagon levels. The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients. Several cardiovascular outcomes trials (CVOTs) have included renal endpoints, adding to the growing evidence of the potential renoprotective effects of these agents in patients with T2DM. Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.

慢性肾脏病（Chronic kidney disease, CKD）是2型糖尿病（type 2 diabetes mellitus, T2DM）的常见并发症，与不良临床结局密切相关，包括全因及心血管死亡风险升高，同时还会带来不利的经济与社会负担。延缓CKD的发生与进展，仍是T2DM患者尚未满足的临床需求。钠-葡萄糖协同转运蛋白2（sodium-glucose co-transporter 2, SGLT2）抑制剂被广泛用于T2DM的临床管理，其作用不仅限于降糖，还兼具心血管获益与潜在肾脏保护作用。尽管这类药物的降糖疗效依赖于肾功能，但SGLT2抑制的心血管与肾脏获益，在估算肾小球滤过率低至30 mL/min/1.73 m²时仍可维持。临床证据表明，这类药物可通过多种机制降低白蛋白尿——一种肾损伤标志物——的发生或恶化风险，具体机制包括：降低血压、减轻肾小球内压与高滤过状态、调控炎症进程、减轻缺血相关肾损伤，以及升高胰高血糖素水平。SGLT2抑制剂的降压作用在CKD患者中依然有效，可进一步减轻肾脏负荷，还可能与这类患者的降压治疗产生协同效应。多项心血管结局试验（cardiovascular outcomes trials, CVOTs）纳入了肾脏终点，进一步丰富了这类药物在T2DM患者中潜在肾脏保护作用的研究证据。多项正在进行的专门肾脏结局试验，将为SGLT2抑制剂在延缓T2DM患者肾损伤发生与进展中的潜在临床应用价值提供更多指导依据。