March 01, 2019
2 min read

PPI therapy fails to improve glycemic response in type 2 diabetes

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A cohort of veterans with type 2 diabetes prescribed proton pump inhibitor therapy experienced a slight improvement in HbA1c that was similar to matched controls not prescribed the medication during the same period, according to findings from a database analysis published in Metabolic Syndrome and Related Disorders.

Six recent studies with small numbers of participants with type 2 diabetes have demonstrated a slightly lower HbA1c among adults prescribed a proton pump inhibitor (PPI) when compared with those not prescribed a PPI, Kelly Villegas, PharmD, a pharmacy practice resident at the Veterans Affairs Northern California Health Care System, and colleagues wrote in the study background.

“Because PPIs lower gastric acid, subsequently increasing gastrin levels, it is theorized that this may stimulate beta-cell proliferation and function and improve glycemic control,” Villegas and colleagues wrote.

In a retrospective study, researchers analyzed data from 2,525 adults with type 2 diabetes from the VA Northern California Health Care System, which includes facilities in northern Nevada, central and northern California, Hawaii and the Philippines (mean age, 67 years; 96% men; mean baseline HbA1c, 7.3%). Within the cohort, 195 patients received a PPI prescription between 2005 and 2011, taken concurrently with stable doses of metformin or sulfonylurea monotherapy. Veterans prescribed insulin, combination antihyperglycemic therapy or oral corticosteroids were excluded. Veterans in the control group received care during the same timeframe and met the same criteria, but were not prescribed a PPI (n = 2,330). Researchers assessed the effect of PPI therapy on glycemic control by comparing HbA1c before and after PPI initiation with the HbA1c of controls. Patients were required to be prescribed a PPI for at least 90 days to determine an effect on HbA1c.

Researchers also assessed factors known to affect glycemic control, including prescriptions for an atypical antipsychotic, niacin, statin therapy or thiazide diuretic, as well as BMI changes and serum potassium levels.

Researchers observed a decrease in HbA1c across both groups of patients, with patients assigned a PPI experiencing a mean 0.32% decrease (P < .001) and controls experiencing a mean 0.27% decrease (P < .001). However, researchers did not observe a between-group difference in HbA1c after treatment. BMI also fell slightly for patients prescribed a PPI and controls; however, there was no between-group difference after treatment.

Additionally, there were no between-group differences in serum potassium levels or the use of other medications known to affect glycemic control between treatment and control groups. Dietary intake was similar between groups, according to the researchers.


The researchers noted that there have been conflicting findings regarding any association between PPI therapy and glycemic response in adults with type 2 diabetes.

“These discrepant results, based on literature review, are testimony to what may be, at most, a modest and inconsistent effect of PPI (therapy) on glycemic control, dependent on study design and patient selection,” the researchers wrote. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.