Abstract
BACKGROUND: Testosterone deficiency is common in men with diabetes. Effects of testosterone therapy on kidney failure and cardiovascular outcomes in diabetic men remain poorly understood. Our aim was to assess whether testosterone therapy is associated with reduced risk of acute kidney injury and kidney failure requiring replacement therapy in men with diabetes and hypogonadism compared to matched untreated men with diabetes. METHODS: Participants were recruited from the TriNetX Research Collaborative network. We identified 26,027 diabetic men with hypogonadism treated with testosterone and matched them 1:1 using propensity score matching to 26,027 untreated diabetic men with hypogonadism. Primary outcomes were acute kidney injury and kidney failure requiring replacement therapy (dialysis or transplantation). Secondary outcomes included myocardial infarction, ischemic stroke, atrial fibrillation, and all-cause mortality. Cox proportional hazard models were used over a mean follow-up of 3.3 years. RESULTS: Men had a mean age of 58 years (SD 12), with 71% being non-Hispanic White. Testosterone-treated men had significantly lower risk of acute kidney injury (HR: 0.93 [95% CI 0.87-0.98], p = 0.01) and kidney failure with replacement therapy (HR: 0.81 [95% CI 0.72-0.92], p = 0.001) compared to untreated men. Testosterone therapy was also associated with reduced risk of myocardial infarction (HR: 0.85 [95% CI 0.78-0.93], p < 0.0001), ischemic stroke (HR: 0.88 [95% CI 0.80-0.97], p = 0.01), atrial fibrillation (HR: 0.91 [95% CI 0.85-0.98], p = 0.01), and all-cause mortality (HR: 0.85 [95% CI 0.79-0.91], p < 0.0001). CONCLUSIONS: In this large real-world cohort study, testosterone therapy in diabetic men with hypogonadism was associated with significant reductions in acute kidney injury, kidney failure requiring replacement therapy, major cardiovascular events, and total mortality. These findings suggest that testosterone therapy could be more readily considered for men with diabetes and hypogonadism as a potential intervention to prevent kidney injury.