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Chinese researchers drew on information from studies of more than 200,000 U.S. health care professionals and found that regular use of PPIs (such as Aciphex, Nexium, Prilosec, Prevacid, Protonix) was associated with a 24% higher risk of developing type 2 diabetes.
"Regular PPI use was likely to be associated with an increased risk of type 2 diabetes, particularly for those with prolonged use," the authors wrote in the report published online Sept. 28 in the journal Gut.
Jinqiu Yuan, a researcher from the Sun Yat-Sen University, Shenzhen, Guangdong, China, led the study.
PPIs are available by prescription or over-the-counter to treat acid reflux, peptic ulcers and other digestive conditions. They are among the top 10 drugs used worldwide. Long-term use has previously been linked to a greater risk of bone fractures, kidney disease, digestive tract infections and stomach cancer.
It's important to note, however, that this study was not designed to prove a cause-and-effect relationship between PPIs and type 2 diabetes. It can only show a link between the two.
The researchers relied on data from three long-term studies of U.S. health professionals that began in the 1970s and 1980s. They included more than 176,000 women and nearly 29,000 men.
Participants provided information on their health and behaviors every two years. In the early 2000s, the questions expanded to include whether they had used a PPI two or more times a week.
Besides linking regular use of PPIs to an increased risk of type 2 diabetes, the researchers found that long-term use increased the odds, too. Study participants who used PPIs for up to two years had a 5% increased risk, and the risk rose 26% for those who took the drugs more than two years.
The study authors also noted that when people stopped taking these drugs, the risk of diabetes fell, and it continued to do so even more over time.
It's unclear exactly how taking acid-reducing medications might increase diabetes risk, the researchers said. One possible way might be through altering the body's natural balance of bacteria (microbiome), they suggested. Another possibility: PPI use may lead to weight gain that can increase the odds of diabetes. More research is needed.
Dr. David Bernstein, a digestive disease specialist from Northwell Health in Manhasset, N.Y., reviewed the findings.
"PPIs are the most effective therapies for the treatment of acid reflux, gastritis and peptic ulcers," Bernstein said. "When first introduced, they were considered 'miracle' drugs as they alleviated previously refractory abdominal pains."
Unfortunately, as the study authors noted, these drugs have been linked to some serious long-term side effects.
"This report, despite its weaknesses, adds yet another potential consequence to an already growing list of medical conditions associated with long-term PPI use," Bernstein said. Weaknesses included the observational nature of the study and lack of randomized comparison groups, he noted.
Still, based upon the findings, it seems reasonable to check patients who have been taking PPIs for more than two years for development of diabetes at regular intervals, he said. "Further studies are required to determine what that interval should be," Bernstein explained.
Another digestive disease specialist, Dr. Arun Swaminath, from Lenox Hill Hospital in New York City, agreed that the study had limitations.
"The main limitation of the study is that the true estimation of PPI exposure is based on memory and recall bias," he said.
But, due to this study's findings and other associated risks of long-term PPI use, Swaminath said, "it's reasonable to always see if a patient still needs their PPI" or if their dose could be lowered.
For those who need to stay on PPIs, doctors and patients need to discuss the drugs' risks and benefits, he advised. Because PPIs are available over-the-counter, "it will not be a simple process to identify all at-risk patients," Swaminath pointed out.
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