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Objective: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE., Methods: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis., Results: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups., Conclusion: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)