Radical cystectomy (RC) with urinary diversion is the standard treatment for muscle-invasive bladder cancer [1]. However, RC is associated with significant perioperative and long-term complications, including metabolic acidosis [2]. This complication arises from urine exposure to the intestinal mucosa of the urinary diversion, leading to chloride absorption and bicarbonate loss [2].

Metformin, commonly prescribed for type 2 diabetes, has been associated with acidosis, particularly in patients with compromised kidney function[3,4]. Notably, these risk factors associated with metformin-induced acidosis are often found in patients after RC due to nephrotoxic chemotherapy, age-related changes, ureteroenteric strictures, obstruction, infection, sepsis, and hypovolemia [[5], [6], [7]].

Furthermore, diabetes itself increases the risk of metabolic acidosis after RC, with its impact growing over time postsurgery [8]. Diabetic patients are also prone to type 4 renal tubular acidosis, which can occur even with mild nephropathy [9,10], and the level of acidosis in these patients can be disproportionately severe to renal function [11].

Interestingly, although diabetic patients generally develop less severe metabolic acidosis due to efficient extrarenal bicarbonate generation [12], this may not apply to those with urinary diversions. Experimental studies have shown increased Na+-K+ ATPases in the ileal mucosa of diabetic rats, suggesting different behavior of intestinal reservoirs in diabetic patients [[13], [14], [15]].

The combination of risk factors associated with RC, chronic kidney disease (CKD), metformin use, and diabetes, which are common in urothelial cancer patients [16], may substantially increase metabolic acidosis risk. This complex interplay necessitates a thorough investigation of metformin's role in metabolic acidosis risk for diabetic patients undergoing RC with urinary diversion.