Pancreatic Safety of Sitagliptin in the TECOS Study

被引：54

作者：

Buse, John B. ^{[1
]}

Bethel, M. Angelyn ^{[2
]}

Green, Jennifer B. ^{[3
]}

Stevens, Susanna R. ^{[3
]}

Lokhnygina, Yuliya ^{[3
]}

Aschner, Pablo ^{[4
]}

Grado, Carlos Raffo ^{[5
]}

Tankova, Tsvetalina ^{[6
]}

Wainstein, Julio ^{[7
]}

Josse, Robert ^{[8
]}

Lachin, John M. ^{[9
]}

Engel, Samuel S. ^{[10
]}

Patel, Keyur ^{[11
]}

Peterson, Eric D. ^{[3
]}

Holman, Rury R. ^{[2
]}

机构：

[1] Univ N Carolina, Sch Med, Chapel Hill, NC 27514 USA

[2] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England

[3] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA

[4] Pontificia Univ Javeriana, Hosp Univ San Ignacio, Bogota, Colombia

[5] Ctr Reg CINVEC, Vina Del Mar, Chile

[6] Med Univ, Univ Specialized Hosp Act Treatment Endocrinol, Sofia, Bulgaria

[7] E Wolfson Med Ctr, Holon, Israel

[8] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada

[9] George Washington Univ, Biostat Ctr, Rockville, MD USA

[10] Merck & Co Inc, Kenilworth, NJ USA

[11] Univ Toronto, Hlth Network, Div Gastroenterol, Toronto Ctr Liver Dis, Toronto, ON, Canada

来源：

DIABETES CARE | 2017年 / 40卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CARDIOVASCULAR OUTCOMES; CANCER; INHIBITORS;

D O I：

10.2337/dc15-2780

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE Weevaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i). RESEARCH DESIGN AND METHODS In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly. RESULTS Baseline differences were minimal between participants confirmed to have no pancreatic events, acute pancreatitis, or pancreatic cancer. Among those participants randomized to receive sitagliptin, 23 (0.3%) (vs. 12 randomized to receive placebo [0.2%]) had pancreatitis (hazard ratio 1.93 [95% CI 0.96-3.88], P = 0.065; 0.107 vs. 0.056/100 patient-years), with 25 versus 17 events, respectively. Severe pancreatitis (two fatal) occurred in four individuals allocated to receive sitagliptin. Cases of pancreatic cancer were numerically fewer with sitagliptin (9 [0.1%]) versus placebo (14 [ 0.2%]) ( hazard ratio 0.66 [95% CI 0.28-1.51], P = 0.32; 0.042 vs. 0.066 events/100 patient-years). Meta-analysis with two other DPP-4i cardiovascular outcome studies showed an increased risk for acute pancreatitis (risk ratio 1.78 [95% CI 1.13-2.81], P = 0.01) and no significant effect for pancreatic cancer (risk ratio 0.54 [95% CI 0.28-1.04], P = 0.07). CONCLUSIONS Pancreatitis and pancreatic cancer were uncommon events with rates that were not statistically significantly different between the sitagliptin and placebo groups, although numerically more sitagliptin participants developed pancreatitis and fewer developed pancreatic cancer. Meta- analysis suggests a small absolute increased risk for pancreatitis with DPP- 4i therapy.

引用

页码：164 / 170

页数：7

共 12 条

[1]

Andersen DK, 2013, PANCREAS, V42, P1227, DOI 10.1097/MPA.0b013e3182a9ad9d

[2] One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice [J].