Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana.
Melvin and Bren Simon Cancer Center, Indiana University, Indiana.
Pharmacoepidemiol Drug Saf. 2020 Feb;29(2):161-172. doi: 10.1002/pds.4943.
This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM).
Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence.
Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence).
Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.
本研究旨在系统评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂与 2 型糖尿病（T2DM）患者胰腺安全性之间的关联。
在 2019 年 9 月之前，检索电子数据库，纳入报告 SGLT2 抑制剂治疗 T2DM 患者发生胰腺炎或胰腺癌任何事件的随机对照试验（RCT）。使用 Peto 比值比（OR）及其 95%置信区间（CI）来汇总数据。引入 GRADE 框架来评估证据质量。
纳入的 35 项 RCT 共涉及 44912 例 T2DM 患者，报告了 41 例急性胰腺炎事件（19 项试验，32932 例患者），72 例总胰腺炎事件（包括急性胰腺炎、慢性胰腺炎或非特异性胰腺炎，26 项试验，36688 例患者），40 例胰腺癌事件（18 项试验，27806 例患者），中位随访时间为 52 周。与对照组（安慰剂或其他活性药物）相比，SGLT2 抑制剂与急性胰腺炎风险增加无关（Peto OR，1.13；95%CI，0.60-2.13；中等质量证据）。对于总胰腺炎（Peto OR，1.08；95%CI，0.67-1.75；中等质量证据）和胰腺癌（Peto OR，1.34；95%CI，0.71-2.54；极低质量证据）风险也得到了类似的结果。
来自 RCT 的中等质量证据表明，SGLT2 抑制剂与急性胰腺炎风险增加无关，而极低质量证据表明 SGLT2 抑制剂与 T2DM 患者的胰腺癌之间无显著关联。
