BACKGROUND Glucose absorbed from conventional peritoneal dialysis (PD) solutions contributes to unfavorable metabolic effects. Its replacement with a glucose-free osmotic agent such as icodextrin (ID) or amino acids (AA) may have some benefit on glucose and lipid metabolism. METHODS Serum lipids, insulin sensitivity and substrate oxidation (calorimetry) were measured before and after 8 weeks use of ID or AA in 22 patients. Calorimetry and blood tests (HbA1c, lipids) were also performed after 8 weeks of simultaneous use of ID and AA in 8 patients. RESULTS Cholesterol declined during the use of AA (4.8 +/- 0.3-4.5 +/- 0.3 mmol/l, p = 0.045). Triglycerides decreased during the use of both ID (2.2 +/- 0.2-1.9 +/- 0.1 mmol/l, p = 0.019) and AA (1.9 +/- 0.2-1.6 +/- 0.1 mmol/l, p = 0.024). Free fatty acids declined during the use of AA. There were no significant changes in insulin sensitivity. Glucose oxidation decreased and lipid oxidation increased during the use of ID, the changes in substrate oxidation were accentuated during the simultaneous use of ID and AA. CONCLUSIONS Replacement of glucose with ID or AA had a benefit on glucose and lipid metabolism.