Compared with DPP-4i, the insulin group developed acute pancreatitis 0.48 years (P < 0.01) earlier and the GLP-1RA group developed pancreatic cancer 3 years later (P < 0.01).
There were no significant differences in all-cause mortality (RR=1.03, 95% confidence interval [CI]=0.95-1.12), cardiovascular mortality (RR=1.02, 95% CI=0.92-1.12), myocardial infarction (RR=0.98, 95% CI=0.89-1.08), strokes (RR=1.02, 95% CI=0.88-1.17), renal failure (RR=1.06, 95% CI=0.88-1.27), severe hypoglycaemia (RR=1.14, 95% CI=0.95-1.36) and pancreatic cancer (RR=0.54, 95% CI=0.28-1.04) with the use of DPP-4Is.
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).
Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia.