Post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes

Background: The long-term effects of the selective estrogen-receptor modulator raloxifene hydrochloride on glycemic control and markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes mellitus are unknown. Objective: The aim of this analysis was to compare the effects of 3-year treatment with raloxifene 60 mg/d versus placebo on glycemic control and markers of cardiovascular disease risk in osteoporotic postmenopausal women with and without type 2 diabetes. Methods: In this analysis, we included women from the Multiple Outcomes of Raloxifene Evaluation trial (a multicenter, double-masked trial) who were randomized to receive raloxifene 60 mg/d (n = 2557) or placebo (n = 2576). Baseline and 36-month fasting plasma glucose (FPG) and total cholesterol (TC) were measured for all participants. Glycated hemoglobin (HbA_1c), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein (apo) A-I, apo B, and fibrinogen were assessed in ∼1800 participants from selected larger sites. Results: At baseline, 202 of all 5133 women (3.9%) had type 2 diabetes. Of the ∼1800 women who were assessed for HbA_1c, LDL-C, TGs, apo A-I, apo B, and fibrinogen, 70 (3.9%) had type 2 diabetes at baseline. Compared with placebo, raloxifene did not significantly affect HbA_1c, FPG, HDL-C, or TGs in women with or without diabetes. Raloxifene produced statistically significant reductions in TC, LDL-C, and fibrinogen both in women with diabetes (all P ≤ 0.004) and without diabetes (all P < 0.001). Raloxifene significantly increased apo A-I (P < 0.001) and reduced apo B (P < 0.001) in women without diabetes. In the raloxifene-treated group, body weight increased by a mean 0.31 kg (P < 0.001) in women without diabetes. Conclusions: In osteoporotic postmenopausal women with or without type 2 diabetes, raloxifene 60 mg/d did not affect glycemic control and had favorable effects on TC, LDL-C, and fibrinogen levels.