Association of preadmission metformin use and prognosis in patients with sepsis with diabetes: a systematic review and meta-analysis.

Abstract

Preadmission metformin may lower mortality in diabetic sepsis patients, but evidence is conflicting, necessitating a systematic review and meta-analysis for confirmation. We systematically searched MEDLINE (via PubMed), EMBASE, and Cochrane CENTRAL from inception to September 1, 2025, for cohort studies evaluating metformin use in septic patients with diabetes. Study quality was assessed using the Newcastle-Ottawa Scale. Two reviewers independently screened studies, extracted data, and evaluated methodological quality. Meta-analysis was conducted using STATA statistical software and Review Manager software, calculating pooled odds ratios with 95% confidence intervals via the inverse variance random-effects model. The MET group included diabetic sepsis patients with preadmission metformin exposure, and the NM group included those without. This meta-analysis of 14 studies (12,687 patients), all with low bias risk, demonstrated that preadmission metformin use in sepsis-diabetes patients was associated with reduced overall mortality (OR 0.58, 95% CI 0.44-0.75, P < 0.00001). Significant reductions were observed in 28-day (OR 0.61, P = 0.002), 90-day (OR 0.48, P = 0.001), 365-day (OR 0.33, P = 0.0005), and in-hospital mortality (OR 0.43, P < 0.02). However, 30-day (OR 0.71, P = 0.06), 60-day (OR 0.72, P = 0.22), and ICU mortality (OR 0.76, P = 0.25) showed no significant differences. Notably, metformin also significantly improved serum creatinine (MD -0.32, P = 0.04) and metformin usage was associated with elevated serum lactate levels. This meta-analysis links preadmission metformin use in diabetic sepsis patients to reduced mortality-particularly 28-day, 90-day, 365-day, and in-hospital-along with decreased serum creatinine. Clinically and from a public health standpoint, these data support the integration of metformin history as a favorable prognostic indicator into updated clinical guidelines, thereby informing future antimicrobial stewardship and sepsis bundle strategies. These findings support further evaluation of metformin's benefits in large-scale, multicenter randomized controlled trials.