Lactate Acidosis Associated with Phenformin Therapy and Localized Tissue Hypoxia

Abstract

The oral hypoglycemic agent phenformin (N¹-β-phenethylbiguanide hydrochloride (DBI⌖¹)) was greeted with hopeful anticipation when Ungar, Freedman, and Shapiro (1) demonstrated its mode of action to be different from the endogenous insulin-stimulating effect of sulfonylureas. Many investigators have reported on the therapeutic efficacy of phenformin, not only in ketoacidosis-resistant diabetes (2, 3), but also as an adjuvant to insulin therapy in juvenile diabetes (4) and in the treatment of insulin resistance (5, 6). It had been observed that patients prone to ketoacidosis could develop ketosis without associated hyperglycemia when treated with prenformin (3, 4, 7). Concern was occasioned by the reports