Diabetes Unit, Department of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Diabetes Care. 2014 Sep;37(9):2435-41. doi: 10.2337/dc13-2546. Epub 2014 Jun 9.
To determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial.
A total of 16,492 type 2 diabetic patients ≥40 years old with established cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo and followed for 2.1 years. Outcome measures were investigator reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer.
Trial investigators reported 35 events of pancreatitis in each treatment arm in 63 patients (33 [0.40%] in the saxagliptin arm and 30 [0.37%] in control arm), with a hazard ratio (HR) of 1.09 (95% CI 0.66-1.79, P = 0.80). Adjudication confirmed pancreatitis in 24 patients (26 events) in the saxagliptin arm (0.29%) and 21 patients (25 events) in placebo arm (0.26%), with an HR of 1.13 (0.63-2.06, P = 0.77). Cases of definite acute pancreatitis were confirmed in 17 (0.2%) vs. 9 (0.1%) (HR 1.88 [0.86-4.41], P = 0.17), definite plus possible pancreatitis in 22 vs. 16 (HR 1.36 [0.72-2.64], P = 0.42), and chronic pancreatitis in 2 vs. 6 (HR 0.33 [0.05-1.44], P = 0.18) in the saxagliptin and placebo arms, respectively. No differences in time to event onset, concomitant risk factors for pancreatitis, investigator-reported causality from study medication or disease severity, and outcome were found between treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively (HR 0.42 [0.13-1.12], P = 0.09).
In the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and apparently similar to placebo, with no sign of increased risk for pancreatic cancer. Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy.
在 SAVOR-TIMI 53 试验中确定胰腺炎和胰腺癌的发病率。
共有 16492 名年龄≥40 岁的 2 型糖尿病患者，患有已确诊的心血管疾病（CVD）或 CVD 危险因素，被随机分配接受沙格列汀或安慰剂治疗，并随访 2.1 年。结局指标由研究者报告，采用盲法专家对总胰腺炎（急性和慢性）和报告的胰腺癌病例进行裁定。
试验研究者报告称，在 63 名患者中，每组各有 35 例胰腺炎事件（沙格列汀组 33 例[0.40%]，对照组 30 例[0.37%]），风险比（HR）为 1.09（95%CI 0.66-1.79，P=0.80）。沙格列汀组有 24 名患者（26 例事件）经裁定证实为胰腺炎（0.29%），安慰剂组有 21 名患者（25 例事件）经裁定证实为胰腺炎（0.26%），HR 为 1.13（0.63-2.06，P=0.77）。确诊为明确性急性胰腺炎的病例分别为 17 例（0.2%）和 9 例（0.1%）（HR 1.88[0.86-4.41]，P=0.17），确诊加可能的胰腺炎病例分别为 22 例和 16 例（HR 1.36[0.72-2.64]，P=0.42），慢性胰腺炎病例分别为 2 例和 6 例（HR 0.33[0.05-1.44]，P=0.18），沙格列汀组和安慰剂组分别为 2 例和 6 例（HR 0.33[0.05-1.44]，P=0.18）。两组间无治疗开始至事件发生时间、胰腺炎的共同危险因素、研究药物引起的因果关系或疾病严重程度以及结局的差异。研究者报告称，沙格列汀组和安慰剂组分别有 5 例和 12 例胰腺癌病例（HR 0.42[0.13-1.12]，P=0.09）。
在 SAVOR-TIMI 53 试验中，2 型糖尿病患者接受沙格列汀治疗 2.1 年内，胰腺炎风险较低，且与安慰剂组相比，风险无明显增加，也未发现胰腺癌风险增加的迹象。需要进一步的研究来彻底解决基于肠促胰岛素的治疗的胰腺安全性问题。
