Impact of Proton Pump Inhibitors on Blood Glucose in Type 2 Diabetes: A Systematic Review with Meta-analysis

Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders, but emerging evidence suggests they may influence glucose metabolism. This meta-analysis evaluates the effect of PPIs on glycemic control in patients with and without type 2 diabetes mellitus (T2DM). We systematically searched PubMed, Cochrane Library, Embase, and Scopus for randomized controlled trials and observational studies reporting fasting blood glucose (FBG), HbA1c, or insulin resistance with PPI use. Risk of bias was assessed using the Cochrane RoB 2.0 tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. Data were synthesized using a random-effects model and expressed as mean differences with 95% confidence intervals (CIs). The review was not prospectively registered in PROSPERO or any other database. Fifteen studies involving 2,038 participants were included in the study. PPI use significantly reduced FBG (mean decrease: 5.32 mg/dL; 95% CI: 2.01-8.63; P = 0.002; 9 studies, n = 1243). HbA1c reductions were observed in some studies (7 studies, n = 1121), but findings were inconsistent. No significant effect was seen on insulin resistance (4 studies, n = 412). Subgroup analyses suggested greater benefits in patients with poorly controlled T2DM. Reported adverse events were mild, including gastrointestinal symptoms and headache. Small sample sizes, study heterogeneity, and moderate risk of bias in some trials limited the certainty of evidence. PPIs may provide modest improvements in glycemic control, particularly among patients with poorly controlled T2DM. While generally safe in the short term, the long-term benefits and risks remain unclear. Regular glucose monitoring may be advisable in diabetic patients on chronic PPI therapy.