Association of metformin administration after septic shock with short-term and long-term survival in septic shock patients with diabetes

Background: In addition to glycemic control, the anti-inflammatory effects and protective effect of metformin on sepsis have been reported in animal studies, which may be beneficial for patients with septic shock. Few observational studies have evaluated metformin administration after sepsis or bacteremia; however, these studies did not specifically analyze septic shock or long-term outcomes. Therefore, this study aimed to evaluate the associations between metformin administration after septic shock and the short- and long-term survival in septic shock patients with type 2 diabetes mellitus. Method: This retrospective observational study used data from a prospectively collected sepsis registry. From October 2016 to June 2022, adult septic shock patients with type 2 diabetes mellitus were included in this study. The variable of interest was metformin administration within 48 h after diagnosis of septic shock. The 90-day mortality and 365-day mortality were evaluated as outcomes. A multivariable Cox proportional hazards model was conducted. Results: A total of 320 patients were included in the study. Metformin administration within 48 h after diagnosis of septic shock was associated with lower 90-day mortality (13.0% vs. 39.8%, P < 0.001), 365-day mortality (23.3% vs. 48.3%, P = 0.001), and in-hospital mortality (9.3% vs. 28.6%, P = 0.002) than those who did not administer metformin within 48 h. Metformin administration within 48 h was independently associated with decreased 90-day mortality (adjusted hazard ratio [aHR]: 0.371, 95% confidence interval [CI]: 0.153–0.900, P = 0.028) and 365-day mortality (aHR 0.453, 95% CI 0.219–0.937, P = 0.033) after adjusting for potential confounders. Similar results were found for metformin administration within 72 h after septic shock (aHR 0.433, 95% CI 0.235–0.797, P = 0.007 for 90-day mortality and aHR 0.450, 95% CI 0.264–0.767, P = 0.003 for 365-day mortality). Conclusions: In septic shock patients with type 2 diabetes mellitus, metformin administration within 48 h was associated with lower 90-day and 365-day mortality. While these findings suggest potential benefits of metformin administration after septic shock, further large, multicenter studies are warranted.