Metformin Use and Clinical Outcomes in Very Elderly Patients with Type 2 Diabetes and Chronic Kidney Disease

Background and Objactives: Metformin is the most widely prescribed glucose-lowering therapy worldwide and is generally considered safe in patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m². However, very elderly patients are underrepresented in pivotal trials, and evidence on metformin safety in this vulnerable population remains limited. We evaluated the association between metformin use and adverse clinical outcomes in very elderly patients with CKD and type 2 diabetes. Materials and Methods: We conducted a single-center retrospective observational study including 624 very elderly patients (age > 78 years) with CKD, type 2 diabetes mellitus, and eGFR > 30 mL/min/1.73 m². Patients were stratified according to metformin exposure (309 metformin-treated and 315 controls). The primary composite outcome was the first occurrence of intensive care unit (ICU) admission, initiation of renal replacement therapy (RRT), lactic acidosis, or all-cause mortality. A propensity score-matched sensitivity analysis and hierarchical win ratio analysis were also performed to further address potential baseline confounding. Results: Over a median follow-up of 33.7 months, the primary composite outcome occurred more frequently in the metformin group than in controls (18.7% vs. 9.5%; HR 1.75; 95% CI 1.12-2.73; p = 0.013). Metformin use was associated with a higher risk of ICU admission (HR 2.33; 95% CI 1.33-4.08), RRT initiation (HR 1.90; 95% CI 1.14-3.16), and lactic acidosis (HR 3.14; 95% CI 1.75-5.65). All-cause mortality was numerically higher but not statistically significant (HR 1.57; 95% CI 0.89-2.78). In a propensity score-matched analysis including 260 matched pairs, the association between metformin exposure and adverse outcomes remained consistent, and hierarchical win ratio analysis favored the control group (win ratio 2.00; 95% CI 1.24-3.47). Conclusions: In very elderly patients with CKD and type 2 diabetes, metformin use was associated with a higher observed risk of adverse clinical outcomes. These findings support a cautious, individualized risk-benefit assessment when prescribing metformin in this population.