西格列汀治疗2型糖尿病的胰腺癌风险评估:来自随机对照试验的荟萃分析结果

doi:10.3969/j.issn.1004-583X.2023.12.001

摘要/Abstract

摘要：

目的评价西格列汀治疗2型糖尿病患者发生胰腺癌的风险。方法计算机检索中国知网,万方,维普,EMBASE, MEDLINE, Web of Science, The Cochrane Library及PubMed数据库,以确定2022年7月10日之前西格列汀治疗2型糖尿病患者与胰腺癌风险相关的研究。采用STATA 12.0软件进行meta分析,由两位研究者独立筛选文献、提取资料及评价纳入文献的质量。结果最终纳入了11项随机对照试验,涉及33360例2型糖尿病患者。固定模型下的meta分析结果显示,西格列汀治疗并未发现胰腺癌风险的增加( $R R$ =0.74,95% $C I$ :0.45~1.21, $P$ =0.225)。亚组分析显示,西格列汀单药治疗( $R R$ =0.82,95% $C I$ :0.39~1.71, $P$ =0.600)和联合治疗方案( $R R$ =0.68,95% $C I$ :0.35~1.31, $P$ =0.244)均未增加胰腺癌的风险。结论西格列汀治疗与胰腺癌风险的增加无关。

关键词: 胰腺肿瘤, 糖尿病,2型, 西格列汀, 荟萃分析

Abstract:

Objective To evaluate the risk of pancreatic cancer (PC) in patients with type 2 diabetes mellitus (T2DM) who are treated with sitagliptin. Methods Articles reporting the risk of PC in T2DM patients treated with sitagliptin published before July 10, 2022 were searched in the online databases, including EMBASE, MEDLINE, the Cochrane Library, PubMed. STATA 12.0 software was used for meta-analysis. Two investigators were independently responsible for article screen, data collection and quality assessment. Results A total of 11 randomized controlled trials involving 33, 360 T2DM patients were identified. Meta-analysis using a fixed-effect model showed that sitagliptin treatment did not significantly increase the risk of PC in T2DM patients ( $R R$ =0.74, 95% $C I$ : 0.45-1.21, $P$ =0.225). Subgroup analyses showed that the monotherapy ( $R R$ =0.82, 95% $C I$ : 0.39-1.71, $P$ =0.600) and combination regimen of sitagliptin ( $R R$ =0.68, 95% $C I$ : 0.35-1.31, $P$ =0.244) did not significantly increase the risk of PC in T2DM patients. Conclusion Sitagliptin treatment is not associated with the increase in the risk of PC.

Key words: pancreatic cancer, diabetes, type 2, sitagliptin, meta-analysis

中图分类号:

R735.9

祝成楼, 吴琼, 达明绪. 西格列汀治疗2型糖尿病的胰腺癌风险评估:来自随机对照试验的荟萃分析结果[J]. 临床荟萃, 2023, 38(12): 1061-1066.

Zhu Chenglou, Wu Qiong, Da Mingxu. Risk assessment of pancreatic cancer in patients with type 2 diabetes mellitus treated with sitagliptin: A meta-analysis of randomized controlled trials[J]. Clinical Focus, 2023, 38(12): 1061-1066.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.12.001

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I12/1061

图/表 6

参考文献 28

[1]	Scott LJ. Sitagliptin: A review in type 2 diabetes[J]. Drugs, 2017, 77(2):209-224. doi: 10.1007/s40265-016-0686-9 pmid: 28078647
[2]	Qaseem A, Barry MJ, Humphrey LL, et al. Oral pharmacologic treatment of type 2 diabetes mellitus: A clinical practice guideline update from the American college of physicians[J]. Ann Intern Med, 2017, 166(4): 279-290. doi: 10.7326/M16-1860 pmid: 28055075
[3]	Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management algorithm-2017 executive summary[J]. Endocr Pract, 2017, 23(2): 207-238. doi: 10.4158/EP161682.CS pmid: 28095040
[4]	Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors[J]. Endocr Rev, 2014, 35(6): 992-1019. doi: 10.1210/er.2014-1035 pmid: 25216328
[5]	Stoian AP, Sachinidis A, Stoica RA, et al. The efficacy and safety of dipeptidyl peptidase-4 inhibitors compared to other oral glucose-lowering medications in the treatment of type 2 diabetes[J]. Metabolism, 2020, 109: 154295. doi: 10.1016/j.metabol.2020.154295 URL
[6]	Scheen AJ. The safety of gliptins: Updated data in 2018[J]. Expert Opin Drug Saf, 2018, 17(4): 387-405. doi: 10.1080/14740338.2018.1444027 URL
[7]	Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment[J]. N Engl J Med, 2014, 370(9): 794-797. doi: 10.1056/NEJMp1314078 URL
[8]	Drucker DJ, Yusta B. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2[J]. Annu Rev Physiol, 2014, 76:561-583. doi: 10.1146/annurev-physiol-021113-170317 pmid: 24161075
[9]	Fujiwara K, Inoue T, Henmi Y, et al. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet[J]. Oncol Lett, 2017, 14(4): 4355-4360. doi: 10.3892/ol.2017.6698 pmid: 28943949
[10]	Charbonnel B, Karasik A, Liu J, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone[J]. Diabetes Care, 2006, 29(12): 2638-2643. doi: 10.2337/dc06-0706 pmid: 17130197
[11]	Raz I, Hanefeld M, Xu L, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus[J]. Diabetologia, 2006, 49(11): 2564-2571. doi: 10.1007/s00125-006-0416-z pmid: 17001471
[12]	Chan JC, Scott R, Arjona Ferreira JC, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency[J]. Diabetes Obes Metab, 2008, 10(7): 545-555. doi: 10.1111/j.1463-1326.2008.00914.x pmid: 18518892
[13]	Goldstein BJ, Feinglos MN, Lunceford JK, et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes[J]. Diabetes Care, 2007, 30(8): 1979-1987. doi: 10.2337/dc07-0627 pmid: 17485570
[14]	Raz I, Chen Y, Wu M, et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes[J]. Curr Med Res Opin, 2008, 24(2): 537-550. doi: 10.1185/030079908X260925 pmid: 18194595
[15]	Arechavaleta R, Seck T, Chen Y, et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: A randomized, double-blind, non-inferiority trial[J]. Diabetes Obes Metab, 2011, 13(2): 160-168. doi: 10.1111/j.1463-1326.2010.01334.x pmid: 21199268
[16]	Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency[J]. Diabetes Care, 2013, 36(5): 1067-1073. doi: 10.2337/dc12-1365 pmid: 23248197
[17]	Henry RR, Staels B, Fonseca VA, et al. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone-a factorial study[J]. Diabetes Obes Metab, 2014, 16(3): 223-230. doi: 10.1111/dom.12194 pmid: 23909985
[18]	Linjawi S, Sothiratnam R, Sari R, et al. The study of once- and twice-daily biphasic insulin aspart 30 (BIAsp 30) with sitagliptin, and twice-daily BIAsp 30 without sitagliptin, in patients with type 2 diabetes uncontrolled on sitagliptin and metformin-The Sit2Mix trial[J]. Prim Care Diabetes, 2015, 9(5):370-376. doi: 10.1016/j.pcd.2014.11.001 pmid: 25488587
[19]	Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2015, 373(3): 232-242. doi: 10.1056/NEJMoa1501352 URL
[20]	Buse JB, Bethel MA, Green JB, et al. Pancreatic safety of sitagliptin in the TECOS study[J]. Diabetes Care, 2017, 40(2): 164-170. doi: 10.2337/dc15-2780 pmid: 27630212
[21]	Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies[J]. Gastroenterology, 2011, 141(1): 150-156. doi: 10.1053/j.gastro.2011.02.018 pmid: 21334333
[22]	Vlavcheski F, O'Neill EJ, Gagacev F, et al. Effects of berberine against pancreatitis and pancreatic cancer[J]. Molecules, 2022, 27(23):8630. doi: 10.3390/molecules27238630 URL
[23]	Tseng CH. Sitagliptin and pancreatic cancer risk in patients with type 2 diabetes[J]. Eur J Clin Invest, 2016, 46(1): 70-79. doi: 10.1111/eci.2016.46.issue-1 URL
[24]	Ohnuma K, Hatano R, Komiya E, et al. A novel role for CD26/dipeptidyl peptidase IV as a therapeutic target[J]. Front Biosci (Landmark Ed), 2018, 23(9):1754-1779. doi: 10.2741/4671 pmid: 29772527
[25]	Mega C, Vala H, Rodrigues-Santos P, et al. Sitagliptin prevents aggravationof endocrine and exocrine pancreatic damage in the zucker diabetic Fatty rat-focus on amelioration of metabolic profile and tissue cytoprotective properties[J]. Diabetol Metab Syndr, 2014, 6:42. doi: 10.1186/1758-5996-6-42
[26]	Gokhale M, Buse JB, Gray CL, et al. Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: A cohort study[J]. Diabetes Obes Metab, 2014, 16(12):1247-1256. doi: 10.1111/dom.12379 pmid: 25109825
[27]	Tseng CH. New-onset diabetes with a history of dyslipidemia predicts pancreatic cancer[J]. Pancreas, 2013, 42(1):42-48. doi: 10.1097/MPA.0b013e3182571ba9 URL
[28]	Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes[J]. Diabetologia, 2009, 52(9):1766-1777. doi: 10.1007/s00125-009-1440-6 pmid: 19572116

第一作者	国家	类型	治疗方案		样本量(PCevents)	疗程(周)
第一作者	国家	类型	干预组	对照组	样本量(PCevents)	疗程(周)
Charbonnel^[10], 2006	法国	RCT	西格列汀+安慰剂	格列吡嗪+安慰剂	464(1) vs 237(0)	104
Raz^[11], 2006	以色列	RCT	西格列汀+安慰剂	吡格列酮+安慰剂	411(0) vs 110(1)	54
Chan^[12], 2008	中国	RCT	西格列汀	安慰剂	65 (1) vs 26 (0)	54
Goldstein^[13], 2007	美国	RCT	西格列汀+二甲双胍	二甲双胍	182(0) vs 176(1)	24
Raz^[14], 2008	以色列	RCT	西格列汀+二甲双胍	安慰剂+二甲双胍	96 (0) vs 94 (1)	30
Arechavaleta^[15], 2011	墨西哥	RCT	西格列汀+二甲双胍	格列美脲+二甲双胍	516(1) vs 518(0)	30
Arjona^[16], 2013	美国	RCT	西格列汀	格列美脲	210(1) vs 212(0)	54
Henry^[17], 2014	美国	RCT	西格列汀+吡格列酮	吡格列酮	231(1) vs 233(0)	54
Linjawi^[18], 2015	阿根廷	RCT	胰岛素+西格列汀+二甲双胍	胰岛素+二甲双胍	193(1) vs 192(0)	24
Green^[19], 2015	美国	RCT	西格列汀	安慰剂	7257(9) vs 7266(14)	260
Buse^[20], 2017	美国	RCT	西格列汀	安慰剂	7332(9) vs 7339(14)	144

第一作者	国家	类型	治疗方案		样本量(PCevents)	疗程(周)
第一作者	国家	类型	干预组	对照组	样本量(PCevents)	疗程(周)
Charbonnel^[10], 2006	法国	RCT	西格列汀+安慰剂	格列吡嗪+安慰剂	464(1) vs 237(0)	104
Raz^[11], 2006	以色列	RCT	西格列汀+安慰剂	吡格列酮+安慰剂	411(0) vs 110(1)	54
Chan^[12], 2008	中国	RCT	西格列汀	安慰剂	65 (1) vs 26 (0)	54
Goldstein^[13], 2007	美国	RCT	西格列汀+二甲双胍	二甲双胍	182(0) vs 176(1)	24
Raz^[14], 2008	以色列	RCT	西格列汀+二甲双胍	安慰剂+二甲双胍	96 (0) vs 94 (1)	30
Arechavaleta^[15], 2011	墨西哥	RCT	西格列汀+二甲双胍	格列美脲+二甲双胍	516(1) vs 518(0)	30
Arjona^[16], 2013	美国	RCT	西格列汀	格列美脲	210(1) vs 212(0)	54
Henry^[17], 2014	美国	RCT	西格列汀+吡格列酮	吡格列酮	231(1) vs 233(0)	54
Linjawi^[18], 2015	阿根廷	RCT	胰岛素+西格列汀+二甲双胍	胰岛素+二甲双胍	193(1) vs 192(0)	24
Green^[19], 2015	美国	RCT	西格列汀	安慰剂	7257(9) vs 7266(14)	260
Buse^[20], 2017	美国	RCT	西格列汀	安慰剂	7332(9) vs 7339(14)	144