Raloxifene Does Not Modify Insulin Sensitivity and Glucose Metabolism in Postmenopausal Women

Abstract

Insulin sensitivity (Si), glucose tolerance, and lipid metabolism were investigated in osteopenic postmenopausal women before and after 6 months of treatment with raloxifene (60 mg/d) or placebo. In a group of women (n = 34), glucose metabolism was evaluated by means of an oral glucose tolerance test (75 g). In another group of women (n = 24), Si and peripheral glucose utilization not dependent on insulin were evaluated by means of a frequently sampled iv glucose tolerance test associated with the minimal model method. No metabolic modification was observed in women receiving placebo. Raloxifene did not significantly modify high density lipoprotein-cholesterol and triglycerides, whereas it significantly decreased low density lipoprotein (LDL) cholesterol (4.84 +/- 0.34 mmol/liter vs. 3.83 +/- 0.49 mmol/liter; P = 0.014) and LDL/high density lipoprotein cholesterol ratio (3.21 +/- 0.31 mmol/liter vs. 2.46 +/- 0.44 mmol/liter; P = 0.012). Fasting levels and responses to the oral glucose tolerance test of glucose, insulin, C-peptide, and C-peptide/insulin were not modified by raloxifene. Similarly, raloxifene did not modify Si (4.22 +/- 4.1 vs. 5.13 +/- 1.75), or insulin (0.025 +/- 0.003 vs. 0.019 +/- 0.002). The present data show that in osteopenic postmenopausal women raloxifene reduces LDL levels but does not modify insulin sensitivity and glucose metabolism.

Raloxifene decreases serum IGF-I in male patients with active acromegaly

“…This is in contrast to the results of other studies (24,25,38,42,43). It is possible that the decrease in insulin sensitivity in our study was due to the higher doses of raloxifene, the shorter period of treatment or the gender of patients.…”

Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women

“…This finding is different from what was observed in the above mentioned study [7], but it has been shown that the insulin to glucose ratio does not correlate with the measurement of insulin sensitivity during the euglycaemic insulin clamp [10]. Our data are also in contrast with those from two recent reports where raloxifene (60 mg/day) resulted in no changes in insulin sensitivity [8] or improvements in gluco-insulinaemic homeostasis [6] respectively. These differences could be due to the different methods of assessment of insulin sensitivity and the shorter duration of raloxifene treatment (12 weeks) used by these studies compared to ours.…”

“…In a 3-year large clinical trial raloxifene seems to increase the risk of new or worsening diabetes [5]. In contrast, insulin sensitivity has been reported as unmodified [6] or even improved [7,8] after raloxifene treatment. Considering these data, we decided to better and specifically investigate the effect of long-term raloxifene administration on glucose metabolism and especially on insulin sensitivity in a group of postmenopausal women.…”

Effect of selective estrogen receptor modulators on metabolic homeostasis

“…In postmenopausal women with or without type 2 diabetes, shortterm raloxifene treatment (12 weeks or 6 months) did not alter fasting blood glucose [49e52] or insulin level [49,50,52] and had no effect on glucose tolerance [49,50] or insulin sensitivity [50e52]. Notably, in a subgroup of patients with hyperinsulinemia, raloxifene significantly reduced plasma insulin by improving fractional hepatic extraction of insulin and peripheral insulin sensitivity [49].…”