Impact of Different Glomerular Filtration Rate Equations on Metformin Eligibility in Patients with Diabetes Mellitus and Chronic Kidney Disease

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Background: Chronic kidney disease (CKD) affects up to 40% of patients with diabetes mellitus and has important implications for metformin safety. Although estimated glomerular filtration rate (eGFR)-based dosing is recommended, there is no consensus on the optimal estimating equation, which may lead to inconsistent treatment decisions. Methods: This retrospective study analyzed 46,788 Thai patients with diabetes from 2014 to 2024. eGFR was calculated using five equations, and CKD stages and metformin eligibility were evaluated according to U.S. FDA and KDIGO guidelines. Results: Median eGFR differed significantly across equations (p-value < 0.001), with the highest values observed using CKD-EPI 2009 and the lowest using Cockcroft–Gault. Among 30,805 metformin users, 0.6–3.7% had eGFR < 30 mL/min/1.73 m2 depending on the equation used. Agreement with CKD-EPI 2009 ranged from 96 to 99 than 1% (≈3% with Cockcroft–Gault) were unnecessarily excluded from metformin therapy. CKD-EPI 2021 yielded approximately 4.5 mL/min/1.73 m2 higher eGFR values, reclassifying 19% of patients to a better CKD stage. Conclusions: Differences among eGFR equations affect CKD staging and metformin eligibility. CKD-EPI 2009, CKD-EPI 2021, S-MDRD, and Thai GFR showed good agreement, whereas Cockcroft–Gault may underestimate renal function, potentially excluding patients who could safely continue metformin. Until outcome data are available, the widely used CKD-EPI equation remains the preferred reference due to its consistency with other standard equations. Further prospective studies are needed to evaluate the clinical impact of equation choice on metformin management.

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