Does preadmission metformin use influence outcomes after sepsis in patients with diabetes? A systematic review and meta-analysis published in Frontiers in Endocrinology found that prior metformin exposure was associated with lower mortality across several clinically relevant timepoints in diabetic patients with sepsis.

The analysis was conducted to address conflicting evidence regarding the relationship between metformin use and mortality in this population. MEDLINE via PubMed, EMBASE, and Cochrane CENTRAL were systematically searched from inception through September 1, 2025, for cohort studies evaluating metformin exposure in septic patients with diabetes. Study quality was assessed with the Newcastle-Ottawa Scale. Two independent assessments were used for study screening, data extraction, and methodological evaluation. Pooled odds ratios with 95% confidence intervals were calculated using an inverse variance random-effects model.

Across 14 studies involving 12,687 patients, overall mortality was lower in patients with preadmission metformin use than in those without prior exposure (OR 0.58; 95% CI 0.44-0.75; P<0.00001). Significant reductions were also reported for 28-day mortality (OR 0.61; P=0.002), 90-day mortality (OR 0.48; P=0.001), 365-day mortality (OR 0.33; P=0.0005), and in-hospital mortality (OR 0.43; P<0.02).

No significant differences were observed for 30-day mortality (OR 0.71; P=0.06), 60-day mortality (OR 0.72; P=0.22), or intensive care unit mortality (OR 0.76; P=0.25). Metformin exposure was also associated with lower serum creatinine levels (MD -0.32; P=0.04), while serum lactate levels were elevated.

From a clinical and public health perspective, the findings support consideration of metformin history as a favorable prognostic indicator in updated guidance, with potential relevance to future antimicrobial stewardship and sepsis bundle strategies. The findings also support further evaluation of metformin in large-scale, multicenter randomized controlled trials.