Kuo Hsiao-Huai, Wang Kuang-Te, Chen Hsin-Hao, Lai Zih-Yin, Lin Po-Lin, Chuang Yung-Jen, Liu Lawrence Yu-Min
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Department of Pharmacy, Hsinchu Municipal MacKay Children's Hospital, Hsinchu, Taiwan.
Diabetol Metab Syndr. 2024 May 22;16(1):108. doi: 10.1186/s13098-024-01354-4.
Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer.
We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity.
Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I = 0%).
SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.
由于存在共同的风险因素以及有充分记录的药物相关心脏毒性，患有糖尿病的癌症患者发生心血管疾病的风险增加。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂已显示出对糖尿病患者的心血管益处，但其对癌症患者的影响仍不清楚。本研究旨在评估SGLT2抑制剂治疗对合并糖尿病和癌症患者心血管结局的影响。
我们对队列研究进行了系统评价和荟萃分析，比较接受SGLT2抑制剂的糖尿病癌症患者与未接受SGLT2抑制剂的患者的心血管结局。从数据库建立至2024年2月29日检索了PubMed、Embase和Cochrane图书馆。主要结局是全因死亡率，次要结局是心力衰竭住院和不良事件。采用随机效应模型计算合并风险比（RR）及95%置信区间（CI）。进行亚组分析和敏感性分析以确定潜在的异质性来源，并探讨SGLT2抑制剂对减轻心脏毒性的作用。
纳入了9项涉及82,654例患者的队列研究。与未使用SGLT2抑制剂相比，使用SGLT2抑制剂与全因死亡率（RR 0.46，95% CI 0.31 - 0.68，P < 0.0001；I² = 98%）和心力衰竭住院率（RR 0.49，95% CI 0.30 - 0.81，P = 0.006；I² = 21%）显著降低相关。在接受蒽环类化疗的患者中，死亡率获益仍然显著（RR 0.50，95% CI 0.28 - 0.89，P = 0.02；I² = 71%）。使用SGLT2抑制剂还与较低的败血症风险（RR 0.32，95% CI 0.23 - 0.44，P < 0.00001；I² = 0%）相关，且糖尿病酮症酸中毒风险未增加（RR 0.66，95% CI 0.20 - 2.16，P = 0.49；I² = 0%）。
SGLT2抑制剂治疗与合并糖尿病和癌症患者的全因死亡率和心力衰竭住院风险较低相关。这些发现表明SGLT2抑制剂可能为这一高危人群带来心血管益处。需要进行随机对照试验来验证这些发现，并评估SGLT2抑制剂在特定癌症类型和治疗方案中的安全性和有效性。
