Introduction Gastroesophageal reflux disease (GERD) is prevalent in patients with type 2 diabetes mellitus (T2DM). The use of proton pump inhibitors (PPIs) is recognized as an effective method to reduce gastric acid secretion in patients with GERD. Nevertheless, whether PPIs are effective or safe for the treatment of T2DM complicated by GERD remains unknown. Material and methods To assess the efficacy and safety of PPIs in the management of T2DM complicated with GERD, databases including Web of Science, Cochrane Library, PubMed, and Embase, were comprehensively searched for randomized controlled trials (RCTs) focusing on the treatment of T2DM complicated with GERD published before December 2023. Following data extraction and quality assessment, outcomes, including endoscopic efficiency, fasting blood glucose (FBG), symptom relief rates, levels of glycosylated hemoglobin A1c (HbA1c), and the incidence of adverse reactions, were analyzed using RevMan 5.4. Results The results suggest that the PPI group exhibited a higher efficacy rate compared to the control group in endoscopic efficiency (69.32% vs. 5.45%, OR: 40.50, 95%CI: 18.77¬–87.39), symptom relief rates (92.94% vs. 54.65%, OR: 6.45, 95%CI: 3.41–12.20). Furthermore, PPI treatment was associated with a significant reduction in HbA1c levels (WMD=-0.41, 95%CI: −0.68 to −0.14) and FBG levels (WMD=−10.15 mg/dL, 95%CI: −19.64 to −0.66) in patients with T2DM complicated with GERD. In terms of safety, the incidence of adverse reactions was not significantly different between the two groups (PPI group: 10.78% vs. control group:11.88%, P>0.05). Conclusions PPIs can effectively improve the glycemic index of patients with T2DM complicated with GERD.
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