Objective: To investigate the effects of tibolone on carbohydrate metabolism, and to compare these effects with those of a sequential regimen of conjugated equine estrogens and medrogestone. Methods: This was an open-label, multicentre, comparative study, Seventy-two postmenopausal women were randomized to receive either tibolone 2.5 mg/day or conjugated equine estrogens 0.6 mg plus sequential medrogestone 5 mg (CEE/M) for six 28-day cycles. Carbohydrate metabolism was evaluated at baseline and after three and six cycles of treatment by an oral glucose tolerance test (OGTT). A blood sample was taken at 30, 60, 90 and 120 mm after glucose 75 mg dosing for determination of plasma glucose, insulin and connecting peptide (C-peptide) levels. Results: The changes from baseline of glucose, insulin and C-peptide area-under-the-curve (AUC) values were not statistically significant after 3 and 6 months of tibolone or CEE/M treatment. There was a small transitory decrease in HbA(1C) after three cycles of treatment with tibolone. Conclusion: The effects of tibolone and CEE/M on carbohydrate metabolism were considered to have no clinical significance. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.