Patients with type 2 diabetes (T2DM) recovering from acute kidney injury (AKI) are at high risk of mortality and progression to chronic kidney disease. Although metformin is widely recommended for its cardiovascular and renal benefits in stable kidney disease, its role during acute kidney disease (AKD) recovery is unclear, given routine discontinuation during acute illness and concerns about safety.

It’s a nationwide target trial emulation using data from the Taiwan National Health Insurance database, including patients with T2DM who suffered from AKI requiring temporary dialysis during hospitalization between January 1, 2015, and September 1, 2020, with follow-up until December 31, 2020. Propensity score matching (PSM), 1:1 was employed to compare outcomes between metformin users and non-users, including all-cause mortality, re-dialysis, major adverse kidney events (MAKE), and major adverse cardiovascular events (MACE), as well as the safety outcome of metabolic acidosis. The target trial emulation was followed the TARGET statement.

Among 11,576 patients (mean age 69.5±12.4, 44.7% male), 3,487 (30.1%) were prescribed metformin following AKI episodes. After PSM, 5,334 patients (mean age 69±12.6, 45.1% male) were equally divided into two groups. Over a mean follow-up of 2.4±1.9 years, metformin use was associated with reduced mortality (hazard ratio [HR] 0.89; 95% CI 0.82–0.97; p = 0.01), re-dialysis (HR 0.69; 95% CI 0.61–0.77; p < 0.001), and MAKE (HR 0.78; 95% CI 0.72–0.84; p < 0.001). The risk of MACE (p = 0.77) was similar between groups, and the risk of metabolic acidosis (p = 0.06) did not increase. External validation showed constant all-cause mortality and kidney benefits. The observed benefits were consistent across all subgroups, with a more pronounced renal benefit among patients who had a baseline or AKD-period estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m². A dose–response pattern was evident, with survival benefits becoming notable at defined daily doses above 27.

Metformin prescription after dialysis-requiring AKI was associated with lower risks of mortality, MAKE, and re-dialysis, without a significant excess in metabolic acidosis among T2DM patients. These findings suggest that cautious reinstatement of metformin may offer meaningful survival and renal benefits in this high-risk population.