Bariatric surgery and changes in metformin distribution: About a fatal case

A 65 year-old woman, suffering from mellitus type 2 diabetes and obesity, died at home, three days after bariatric surgery (Roux-en-Y gastric by-pass: RYGB). Her treatment, including metformin and dapagliflozin, was stopped before surgery and not postoperatively reinstalled. A forensic autopsy, toxicological and histological analyses were performed. No macroscopic or microscopic evidence of digestive perforation or peritonitis was identified, excluding an early surgery complication as the cause of death. Toxicological analysis revealed the presence of Metformin in all matrices tested, with a potentially fatal blood concentration. Death was attributed to lactic acidosis caused by a metformin overdose. With no evidence for suicide by ingestion of metformin, the authors supposed that the bariatric surgery might have caused changes in the absorption of metformin, leading to a rapid overdose and death. The only study in the literature on this subject, demonstrated a significant increase in the bioavailability of metformin following oral administration in gastric bypass patients. Thus, it can be anticipated that a therapeutic dose can become toxic when administrated to a subject who recently modified her digestive equipment. As this represents the first case of metformin overdose following bariatric surgery, further cases will be needed to confirm our initial observations.