The three main concerns regarding the long
safety of the PPIs include the effects
of prolonged hypergastrinemia, the possible association of PPIs with gastric atrophy, and the effects of chronic hypochlorhydria. With omeprazole (prilosec) specifically, there have not been clinically signifcant data extending more than 10 years.
"Current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events.