The effect of raloxifene on glyco-insulinemic homeostasis in healthy postmenopausal women: a randomized placebo-controlled study.

The effect of raloxifene, a selective estrogen receptor modulator recently approved as a therapeutic agent for menopause, on glyco-insulinemic metabolism was investigated in 40 healthy postmenopausal women. At the baseline and after 12 wk of raloxifene (60 mg/d) or placebo administration, all aspects of glucose metabolism were evaluated in each subject using both an oral glucose tolerance test (OGTT; 75 g) and a hyperinsulinemic euglycemic clamp to assess peripheral insulin sensitivity. Glucose, insulin, and C-peptide, measured in fasting conditions, as well as glucose and insulin responses to OGTT [expressed as area under curve (AUC)] were not modified by raloxifene, whereas C-peptide-AUC increased significantly (P < 0.05). Furthermore, a trend toward an improvement of peripheral insulin sensitivity and hepatic clearance of the hormone (fractional hepatic insulin extraction) was observed in the raloxifene-treated women with respect to the control patients. When the subjects were studied in relation to their insulin secretion in response to the glucose load, the patients, classified as hyperinsulinemic, showed the most significant response to the raloxifene treatment. In these women, the selective estrogen receptor modulator was able to induce a significant reduction of insulin circulating plasma values (P < 0.01) through both an increase of fractional hepatic insulin extraction (P < 0.01) and an improvement of the peripheral insulin sensitivity (P < 0.05). On the contrary, no net change of insulin dynamics was observed in normoinsulinemic and placebo-treated women. The present data indicate that raloxifene does not negatively influence glyco-insulinemic metabolism in unselected postmenopausal women and may indeed improve the excessive insulin responsiveness to OGTT in a selected population of hyperinsulinemic postmenopausal women.