Analysis of three prospective studies suggests long-term PPI use could increase the risk of diabetes by more than a quarter, prompting researchers to recommend that people taking these drugs for two years or more undergo regular blood glucose check-ups.
'Owing to wide usage, the overall number of diabetes cases associated with PPI use could be considerable,' they say. 'For patients who have to receive long term PPI treatment, screening for abnormal blood glucose and type 2 diabetes is recommended'.
The researchers, from China and the US, analysed data from three US studies: the Nurses’ Health Study, which began in 1976 (NHS), the NHS II, which began in 1989, and the Health Professionals Follow-up Study (HPFS), which began in 1986.
Starting in 2000 for the NHS, 2001 for NHS II, and 2004 for the HPFS, participants were asked whether they had used PPIs regularly in the preceding 2 years, with regular use defined as twice a week or more.
During the average follow-up period of around 10 to 12 years across the three studies, 10,105 of the 204,689 participants were diagnosed with type II diabetes. The absolute risk of a diagnosis among regular PPI users was 7.44/1000 person–years compared with 4.32/1000 person–years among those who did not take PPIs.
After taking into account potentially confounding factors such as high blood pressure, high cholesterol, physical inactivity and use of other medication, people who regularly used PPIs were 24% more likely to develop type II diabetes than those who did not use the drugs.
The risk of developing diabetes increased with the duration of PPI use: taking the medicines for up to 2 years was associated with a 5% increased risk; taking them for more than 2 years was associated with a 26% increased risk. Conversely, the risk fell the more time had passed since stopping.
Further analysis showed that diabetes risk among PPI users was not affected by sex, age, family history of diabetes, smoking, alcohol intake, diet, physical activity, high cholesterol or regular use of anti-inflammatory drugs, although it was higher among participants who were not overweight or who had normal blood pressure.
For comparison, the researchers also examined the potential impact of H2 antagonists on the development of diabetes. They found that regular use of these drugs was associated with a 14% increased risk and, as with PPIs, longer term use was associated with a higher risk while longer time since stopping was associated with a lower risk.
As an observational study the analysis does not prove causality, but the researchers suggest that changes in the gut microbiome may help explain the association between PPI use and diabetes risk.
Long-term PPI use has previously also been linked to increased risks of hypomagnesaemia and fractures.