Adults with type 2 diabetes who initiate proton pump inhibitor therapy are more likely to experience accelerated diabetes-related renal decline and an increase in 5-year cardiovascular risk compared with those who do not initiate the therapy, according to findings from a longitudinal study in Australia.
“Data from our patients who stopped [proton pump inhibitor] therapy during follow-up provide evidence that the deleterious effects associated with this group of drugs do not persist,” Timothy M.E. Davis, MBBS, DPhil, FRACP, MRCP, professor at the School of Medicine and Pharmacology at Fremantle Hospital, Western Australia, and colleagues wrote. “These data, which are the first that address the potential adverse effects of [proton pump inhibitor] therapy in diabetes, may have implications for the management of type 2 diabetes outside glycemia and non-glycemic CVD risk factors.”
Davis and colleagues analyzed data from patients with type 2 diabetes prescribed stable renin-angiotensin system blocking therapy, recruited between 2008 and 2011 for the Fremantle Diabetes Study Phase II (FDSII). Participants completed questionnaires, physical exams and provided fasting blood samples at baseline, as well as biennial face-to-face assessments and mailed questionnaires. Researchers measured albumin and creatinine concentrations, estimated glomerular filtration rate, and urinary albumin to creatinine ratio.
Researchers stratified participants by four groups: Patients who remained off proton pump inhibitor therapy throughout follow-up (group 1; n = 686); those who remained on proton pump inhibitor therapy throughout follow-up (group 2; n = 174); those who commenced proton pump inhibitor therapy and had a biennial assessment either before or after the change, with an average duration of therapy of at least 12 months (group 3; n = 109); and those who were taking a proton pump inhibitor and had discontinued the medication at the next face-to-face interview, with an average duration off-therapy of at least 12 months (group 4; n = 67). Primary outcomes were changes in urinary albumin to creatinine ratio, changes in eGFR and 5-year CVD risk using a validated prediction equation based on outcome data from the Freemantle Diabetes Study Phase I.
Within the cohort, 342 participants were taking a proton pump inhibitor at baseline (esomeprazole, 36.7%; pantoprazole, 24.9%; omeprazole, 21.1%; rabeprazole, 12.6% and others, 4.7%). Overall mean time between the two FDSII assessments was 2.1 years.
After adjustment for all baseline variables that differed across the four groups, researchers did not observe between-group differences in changes from baseline urinary albumin to creatinine ratio (P .15).
Researchers found that those who initiated proton pump inhibitor therapy (group 3) experienced a greater adjusted mean reduction in eGFR when compared with participants in group 1 (mean, –2.7 mL/min/1.27 m²; P = .005); results persisted after adjusting for baseline variables that differed across groups (P < .2).
Researchers found that the composite, 5-year CVD risk score increased across the four proton pump inhibitor groups during the 2.1 years of follow-up (P < .001). Participants in group 3 who initiated proton pump inhibitor therapy experienced a mean 1.7% increase in CVD risk vs. group 1. The findings paralleled preliminary analyses of self-reported CVD events between the two FDSII biennial assessments, the researchers noted, which were 2.8%, 5.2%, 9.2% and 4.5% in groups 1 through 4, respectively (P = .012).
After adjustment for age, sex and diabetes duration, only group 3 had an increase in 5-year CVD risk when compared with those in group 1 (OR = 3.67; 95% CI, 1.63-8.23).
“The present data provide a note of caution in the context of type 2 diabetes,” the researchers wrote. “Regular assessment of their appropriateness as part of chronic pharmacotherapy as well as regular monitoring of renal function during chronic use appear important, and there is an argument that CVD risk factor management should be optimized if [proton pump inhibitors] are prescribed given the present association with CVD risk after their initiation.” – by Regina Schaffer
: The researchers report no relevant financial disclosures.