Proton pump inhibitors increase CVD, mortality risk for adults with type 2 diabetes
Click Here to Manage Email Alerts
Adults with type 2 diabetes who use proton pump inhibitors have a higher risk for coronary artery disease, myocardial infarction, heart failure and all-cause mortality than nonusers, according to data from the UK Biobank.
“These findings suggest that the clinical benefits of proton pump inhibitor (PPI) use against the excess risks of cardiovascular events and mortality should be taken into consideration among patients with type 2 diabetes,” An Pan, PhD, professor of epidemiology in the School of Public Health at Tongji Medical College, Huazhong University of Science and Technology in China, told Healio. “Physicians should enhance monitoring of CV phenotypes among patients with type 2 diabetes during PPI therapy.”
Pan and colleagues collected data from 19,229 adults with type 2 diabetes who participated in the UK Biobank between March 2006 and October 2010 (mean age, 59.5 years; 59.5% men). Participants self-reported whether they regularly used PPIs, with regular use defined as the taking a medication for most days in a 4-week period. Occurrences of CAD, MI, heart failure, stroke and all-cause mortality were collected from self-reported data, primary care records, hospital admission records and death register records.
The findings were published in The Journal of Clinical Endocrinology & Metabolism.
Of the cohort, 3,275 adults reported using PPIs and 15,954 were nonusers. During follow-up, there were 2,971 cases of CAD, 1,827 cases of MI, 1,192 cases of heart failure, 738 stroke cases and 2,297 participants who died.
In a fully adjusted model, adults who used PPIs had higher risks for CAD (adjusted HR = 1.27; 95% CI, 1.15-1.4) MI (aHR = 1.34; 95% CI, 1.18-1.52), heart failure (aHR = 1.35; 95% CI, 1.16-1.57) and all-cause mortality (aHR = 1.3; 95% CI, 1.16-1.45) compared with those who did not use those medications.
“We did not observe significant associations of PPI use with risk of stroke and CVD mortality, which might be explained by low statistical power due to the modest number of stroke cases and CVD deaths,” Pan said.
In an analysis of different medications, consistent associations for the risk of CAD, MI, heart failure and all-cause mortality were found, though some medications had null associations potentially due to the small number of cases. The main findings were confirmed in sensitivity analysis that used propensity score matching to pair PPI users with nonusers, when participants with less than 2 years of follow-up were excluded and when further adjustments were made for H2 receptor antagonist use.
“In this study, information on frequency, duration and dosage of PPIs use was not collected; hence, future studies are needed to further clarify the relationship between these characteristics and adverse outcomes among patients with type 2 diabetes,” Pan said. “In addition, further trials are warranted on PPI use and CV events and mortality among patients with type 2 diabetes, particularly on whether other drugs could replace PPIs to avoid the adverse CV events.”
For more information:
An Pan, PhD, can be reached at panan@hust.edu.cn.
Perspective
Back to Top
The potential use of existing medications for new indications is always a welcome discovery. In the treatment of diabetes, both bromocriptine and colesevelam were able to demonstrate HbA1c lowering earning them an FDA indication for the treatment of diabetes. Proton pump inhibitors (PPI) increase gastrin levels and are thought to have an incretin-like effect by which they may reduce glucose levels with long-term use. A recent meta-analysis demonstrated a modest reduction in HbA1c of 0.36% with PPI use. This potential benefit may be seen as a stepping stone to a possible new indication for the treatment of diabetes.
However, chronic PPI use is also under scrutiny with potential adverse long-term effects, such as interference with antiplatelet therapy, increased risk for osteoporosis and possibly increasing the risk for chronic kidney disease.
The current study evaluates the use of PPIs and risk for cardiovascular outcomes and all-cause mortality in patients with type 2 diabetes. Utilizing data from the UK Biobank, the investigators were able to show use of PPI in patients with type 2 diabetes was associated with a higher risk for coronary artery disease, myocardial infarction, heart failure, and all-cause mortality.
This highlights the importance of going beyond the surrogate marker of HbA1c lowering and the need to assess for long-term micro- and macrovascular outcomes for diabetes treatments. Contrary to statins — which modestly raise glucose levels, but have a strong track record of reducing CV endpoints — it seems PPIs may modestly lower glucose, but raise CV risk.
Collapse
Click Here to Manage Email Alerts