Short-Term Changes in Glycemic Parameters Following Proton Pump Inhibitor Therapy in Patients With Type 2 Diabetes Mellitus: A Retrospective Cohort Study

PPIs and Glycemic Changes in T2DM

Abstract

Background: Emerging evidence suggests that proton pump inhibitors (PPIs) may influence glucose metabolism through mechanisms such as gastrin-mediated stimulation of pancreatic β-cell activity and alterations in gut microbiota composition. However, clinical studies evaluating the metabolic effects of PPIs in patients with type 2 diabetes mellitus (T2DM) have yielded inconsistent findings. The present study aimed to evaluate short-term changes in glycemic parameters after initiation of PPI therapy in patients with T2DM and to explore clinical characteristics associated with reductions in fasting glucose.
Methods: This retrospective observational study included 66 adults with T2DM who were newly prescribed a PPI in a gastroenterology outpatient setting. Clinical and laboratory data were obtained from electronic medical records and verified through the national prescription monitoring system. Fasting glucose, postmeal glucose, glycated hemoglobin (HbA1c), and body mass index (BMI) were recorded at baseline and during a three-month follow-up period. Changes in glycemic parameters were analyzed using paired statistical tests, and logistic regression was used to identify factors associated with reductions in fasting glucose.
Results: The mean age of participants was 57.93 ± 10.90 years, and the mean BMI was 29.31 ± 2.98 kg/m². During the three-month follow-up period, mean fasting glucose decreased significantly from 132.12 ± 19.61 mg/dL to 122.13 ± 23.52 mg/dL (p < 0.001). Postmeal glucose and HbA1c levels showed numerical reductions but did not reach statistical significance. A decrease in fasting glucose was observed in 47 of 66 participants (71.2%). Patients who experienced fasting glucose reduction were significantly older, had lower BMI, and had a shorter duration of diabetes compared with those without reduction. Multivariate analysis demonstrated that older age, lower BMI, and shorter diabetes duration were independently associated with fasting glucose reduction.
Conclusions: PPI therapy was associated with a modest reduction in fasting glucose during short-term follow-up, whereas HbA1c and postmeal glucose levels did not change significantly. The observed association appeared to vary according to patient characteristics, particularly BMI and duration of diabetes. These findings suggest that metabolic responses to PPI therapy may differ across clinical subgroups of patients with T2DM and warrant further investigation in larger prospective studies.