Proton Pump Inhibitors, Nephropathy, and Cardiovascular Disease in Type 2 Diabetes: The Fremantle Diabetes Study.

Abstract

There is emerging evidence of various adverse effects of chronic proton pump inhibitor (PPI) therapy. To assess the impact of PPI use on nephropathy and cardiovascular disease (CVD) risk in type 2 diabetes. Longitudinal observational study. Urban-dwelling community. Patients with type 2 diabetes from the Fremantle Diabetes Study Phase II and on stable renin-angiotensin system blocking therapy were divided into those remaining untreated with a PPI (group 1, n = 686), on PPI therapy throughout (group 2, n = 174), and commencing (group 3, n = 109) or discontinuing regular PPI therapy (group 4, n = 67) during the 2 years between assessments. Changes (Δ) in urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFR), and predicted 5-year CVD risk. There were no statistically significant differences in ΔuACR between groups [analysis of variance (ANOVA), P = 0.36], but ΔeGFR was different (ANOVA, P = 0.002), with group 3 exhibiting a greater reduction than group 1 [adjusted mean difference (95% confidence interval), -2.7 (-4.5 to -0.8) mL/min/1.73 m2; P = 0.005]. The Δ5-year CVD risk showed a similar pattern (ANOVA, P < 0.001), with group 3 having a greater increase than group 1 [adjusted mean difference (95% confidence interval), 1.7% (0.6% to 2.8%); P = 0.002]. Although PPI use was not associated with a sustained adverse effect on uACR, the association between PPI initiation and both worsening nephropathy and increasing 5-year CVD risk has potential clinical implications in type 2 diabetes.