Chronic Proton Pump Inhibitor Use and Glycemic Control in Older Adults with Type 2 Diabetes Mellitus: A Retrospective Cross-Sectional Study

Background/Objectives: Evidence regarding the effects of proton pump inhibitors (PPIs) on glucose metabolism is conflicting, and real-world data on the association between chronic PPI use and glycemic control in older adults with type 2 diabetes mellitus (T2DM) are limited. This study aimed to evaluate the association between chronic PPI use and glycemic control in patients with T2DM aged 65 years or older. Methods: This single-center, retrospective cross-sectional study included 462 T2DM patients attending the Family Medicine Outpatient Clinic of Ankara Bilkent City Hospital between April 2025 and April 2026. Patients with regular PPI use for ≥6 months before the index HbA1c were classified as chronic PPI users. Suboptimal glycemic control was defined as HbA1c ≥ 8.0%. Associations were evaluated using logistic regression for suboptimal control and linear regression for HbA1c level. Results: Of the 462 patients, 316 (68.4%) were chronic PPI users. Mean HbA1c (7.11 ± 1.21% vs. 6.23 ± 0.99%; p < 0.001) and fasting plasma glucose (148.70 ± 64.87 vs. 116.23 ± 43.54 mg/dL; p < 0.001) were higher among PPI users. In multivariable logistic regression, chronic PPI use was independently associated with suboptimal glycemic control (adjusted odds ratio [aOR] = 3.416; 95% CI: 1.572–7.422; p = 0.002). This association remained significant in a sensitivity model additionally adjusted for age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking status, diabetes duration, insulin use, metformin use, and heart failure/coronary artery disease (aOR = 3.834; 95% CI: 1.734–8.478; p = 0.001). In multivariable linear regression, chronic PPI use was independently associated with a 0.793-percentage-point higher HbA1c level (95% CI: 0.570–1.016; p < 0.001). Conclusions: Chronic PPI use was independently associated with higher HbA1c levels and suboptimal glycemic control in older adults with T2DM. Because of the observational design, causality cannot be established. Prospective studies accounting for PPI indication, agent-specific effects, dose, and duration of exposure are needed to clarify the nature of this association.