Incretin based therapy and pancreatic cancer: Realising the reality

Table 3 Important systematic reviews and meta-analyses which evaluated the relationship between incretin-based therapies and pancreatic cancer

Ref.	Description	Findings
Alves et al[39], 2012	All studies (25 RCT/longitudinal observational) assessing the estimate of pancreatitis/PC in patients with T2DM using exenatide or liraglutide	For PC risk, the OR of exenatide was 0.86 (95%CI: 0.29-2.60) and liraglutide was 1.35 (95%CI: 0.70-2.59)
Chen et al[40], 2016	All RCTs reporting PC with use of incretin-based therapies compared with placebo or non-incretin anti-diabetic drugs in patients with T2DM	Overall, no increased risk of PC was detected in association with incretin-based treatment (RR = 0.7, 95%CI: 0.37–1.05). The incidence of PC was even lower among incretin-based groups than controls (RR = 0.50, 95%CI: 0.29–0.87) in trials with duration more than 104 wk
Zhang et al[41], 2017	6 prospective randomized controlled trials (EXAMINE, SAVOR-TIMI 53, TECOS, ELIXA, LEADER and SUSTAIN-6)-3 trials for DPP-4is and 3 trials for GLP-1 RAs	Incretin-based agents did not significantly affect PC-OR: 0.71 (95%CI: 0.45–1.11)
Pinto et al[42], 2019	12 RCTs with GLP-1 RAs as an intervention, from database inception till 2017	GLP-1 RAs did not increase the risk for pancreatic cancer when compared to other treatments-OR: 1.06 (95%CI: 0.67-1.67)
Abd El Aziz et al[43], 2020	Meta-analysis of cases of acute pancreatitis and PC as well as any malignant neoplasm reported in 11 CVOTs with GLP-1 RAs and DPP-4i	Neither GLP-1 RAs nor DPP-4is were associated with a significantly elevated or reduced risk of PC. For GLP-1 RA OR was 1.14 (95%CI: 0.77-1.7) and for DPP4i OR was 0.94 (95%CI: 0.52-1.68)

PC: Pancreatic cancer; RCT: Randomised controlled trial; T2DM: Type 2 diabetes mellitus; OR: Odds ratio; RR: Risk ratio; CVOT: Cardiovascular outcome trial; GLP-1 RA: Glucagon like peptide-1 receptor agonists; DPP-4i: Dipeptidyl Peptidase-4 inhibitors; OHA: Oral hypoglycemic agent.