Incretin based therapy and pancreatic cancer: Realising the reality

Table 2 Important observational studies which evaluated the relationship between incretin-based therapies and pancreatic carcinoma

Ref.	Study design	Population	Findings
Elashoff et al[6], 2011	Retrospective study (Control drugs-rosiglitazone, glinides, glipizide), 2004-09	Database-FDA AERS. Patients of T2DM on exenatide and sitagliptin. n = 1541 events (exenatide). n = 322 (sitagliptin). n = 691 (controls)	PC was more common among patients who took sitagliptin (2.7-fold) or exenatide (2.9-fold) as compared with other therapies
Montvida et al[34], 2019	Retrospective record-based study. 2005 onwards. Follow-up duration 2.27-4.3 yr	Centricity electronic medical record, United States. DPP-4i n = 50095. GLP-1 RA n = 12654. SU n = 110747. TZD n = 17597. Insulin n = 34805	Compared with DPP-4i, the GLP-1 RA group developed PC 3 yr later (95%CI: 0.84-5.16). No other significant differences were observed between groups
Nagel et al[35], 2016	Retrospective study (Control drugs-rosiglitazone, glinides, glipizide), 1968-2013	Database-FDA AERS. Patients of T2DM on sitagliptin, saxagliptin, linagliptin, and alogliptin. n = 156 PC patients	EB05 was 10.3 for sitagliptin, 7.1 for saxagliptin, 4.9 for linagliptin, and 1.4 for alogliptin, compared with all other agents
Azoulay et al[36], 2016	Nested case control analysis (control drug- sulfonylureas), 2007-2014. Follow-up 1.3-2.8 yr	Database-CNODES (Canada, United States, United Kingdom). n = 972384	Compared with SUs, incretin-based drugs were not associated with an increased risk of PC-pooled aHR 1.02 (95%CI: 0.84-1.23)
Tseng et al[37], 2017	Retrospective population-based cohort study, 1997-2010. Follow up-till occurrence of adverse pancreatic event	Database-The Taiwan National Health Insurance Research Database. n = 13171 incretin. n = 13171 non-incretins	PC occurred in 6 (0.05%) and 10 (0.08%) patients in the incretin and non- incretin cohort, respectively
Boniol et al[38], 2018	Retrospective cohort study, 2008-2013. Follow-up 1.8-2.3 yr	Public health insurance databases of Belgium, Lombardy (Italy). n = 33292 incretin. n = 525733 control	The aHR for PC was 2.14 (95%CI: 1.71–2.67) for incretin group compared with control

FDA AERS: Food and drug administration adverse event reporting system; T2DM: Type 2 diabetes mellitus; PC: Pancreatic carcinoma; EB05: Empirical Bayesian fifty centile; aHR: Adjusted hazard ratio; CI: Confidence interval; CNODES: Canadian network for observational drug effect studies; SU: Sulfonylurea; OHA: Oral hypoglycemic agent; RR: Risk ratio; TZD: Thiazolidinedione.