Dicarboxylic acids have been proposed as an alternate lipid energetic substrate for total parenteral nutrition. No data are yet available on the possible effect of dicarboxylic acids on glucose metabolism in humans. Thus, we examined the effect of a continuous intravenous infusion of the sodium salt of the10‐carbon atom alyphatic dicarboxylic acid, sebacate (Sb), on insulin‐dependent glucose metabolism in four control subjects, four patients with insulin‐dependent diabetes mellitus, and four obese subjects. All subjects received a constant 5‐hour infusion of saline or sebacate (6.6 g/h), in a randomized order on two different days. After 3 hours of infusion, a 120‐minute euglycemic, hyperinsulinemic clamp procedure was performed (insulin infusion rate = 40 mU/m2per minute). Glucose uptake, plasma sebacate, insulin, glucagon, C‐peptide, and ketone bodies were measured. No significant differences in insulinemia were found among groups either during the saline infusion or the sebacate infusion. On the contrary, glucose uptake (molar) was significantly reduced during the sebacate vs the saline day in all three groups: 6.7 ± 0.04vs3.7 ± 1.3 in control subjects (p<.001), 4.6 ± 0.4vs2.5 ± 1.2 in patients with insulin‐dependent diabetes mellitus (p<.001), and 4.8 ± 0.5vs2.7 ± 0.2 mg/kg per minute in obese subjects (p<.001). In conclusion, Sb administration was associated with a glucose‐sparing effect as shown by the reduced glucose uptake in all patients studied. Sebacate did not stimulate insulin secretion, inasmuch as no modification of C‐peptide plasma levels was observed after 3 hours of Sb infusion. In addition, no change in Sb steady‐state levels was observed during hyperinsulinemia, suggesting that insulin does not influence Sb plasma clearance. (Journal of Parenteral and Enteral Nutrition18:9–13, 1994)