Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia

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Abstract
Dichloroacetate is known to reduce plasma glucose and triglycerides in diabetic and starved animals and to lower plasma lactate under various experimental conditions. To investigate its metabolic effects in man, we administered oral doses (3 to 4 g) of dichloroacetate as the sodium salt to patients with diabetes mellitus or hyperlipoproteinemia or both for six to seven days. Dichloroacetate significantly reduced fasting hyperglycemia an average of 24 per cent (P<0.01) from base line and produced marked, concomitant falls in plasma lactate (73 per cent; P<0.05 to <0.01) and alanine (82 per cent; P<0.01 to <0.001). In addition, it significantly decreased plasma cholesterol (22 per cent; P<0.01 to <0.001) and triglyceride (61 per cent; P<0.01) levels while increasing (71 per cent; P<0.01) plasma ketone-body concentrations. Plasma insulin, free fatty acid and glycerol levels were not affected. Serum uric acid rose, whereas excretion and renal clearance fell. Some patients experienced mild sedation, but no other laboratory or clinical evidence of adverse effects was noted during or immediately after the treatment phase. (N Engl J Med 298:526–530, 1978)