Will Proton Pump Inhibitors Increase the Risk of Diabetes Mellitus? A Systemic Review and Meta-Analysis.

BACKGROUND: Proton pump inhibitor use was reported to potentially provide benefits to prevent diabetes mellitus. This study aims to investigate the association between proton pump inhibitor use and the risk of developing diabetes mellitus. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021238481). A systematic literature search was conducted to identify eligible studies up to February 2021. Quality assessment was conducted according to Jadad Scoring Scale and Newcastle-Ottawa Scale. The heterogeneity among studies was tested and estimated by Q test and I2. Pooled hazard ratio with 95% CI was calculated using the random-effects or fixed-effects model depending on the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also performed. RESULTS: Eight studies including 850 019 participants were included. We found that proton pump inhibitor use was associated with a statistically non-significant increased risk of diabetes mellitus (pooled hazard ratio was 1.06, 95% CI = 0.89-1.28, P = .50). In subgroup analysis, 5 studies conducted in North America confirmed the overall result; however, one study conducted in Europe demonstrated a statistically significant increased risk, while one study in Asia revealed a statistically significant decreased risk. CONCLUSION: Proton pump inhibitor use is not associated with either increased or decreased risk of diabetes mellitus. However, more well- designed studies focusing on proton pump inhibitor use and the risk of diabetes mellitus, especially among populations with different backgrounds, are still needed.

Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. METHODS AND RESULTS: Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. CONCLUSION: Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. REGISTRATION NUMBER: PROSPERO-CRD42020221951.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.