MON-160 Effect Of The Combination Conjugated Estrogens And Bazedoxifene On Glucose Homeostasis In Obese Postmenopausal Women: A Placebo-controlled Randomized Pilot Trial

Background and Objectives: Randomized controlled trials suggest that menopausal estrogen therapy reduces the incidence of type 2 diabetes (T2D). The combination conjugated estrogens (CE) and the selective estrogen receptor modulator, bazedoxifene (BZA) is a menopausal therapy. In a mouse model, the combination CE/BZA prevented estrogen deficiency-induced obesity, insulin resistance and T2D, as efficiently as CE alone. The objective of this study was to assess the effect of CE/BZA on glucose homeostasis and body composition in obese post-menopausal women. Methods: Randomized double blind placebo-controlled pilot trial in 12 obese post-menopausal women (mean age 54.7± 2.3 years, BMI 34.0±4.4 kg/m(2), years since LMP 3.0±1.5) assigned to 12 weeks of treatment with placebo or CE/BZA. At baseline and after 12 weeks, we performed IV-glucose tolerance test (IVGTT) and measured serum adipokines and inflammatory biomarkers (leptin, adiponectin, FGF-21, LCN2, RBP4, CRP, PAI-1 and TBARS) to assess glucose homeostasis and inflammation respectively. Wilcoxon rank sum tests were used to test for differences between treatment arms in the mean change in outcomes from baseline to final study visit. Results: Minimal model analysis of IVGTT revealed decreased basal glucose concentration (Gb) and increased beta cell function in CE/BZA treated subjects compared to placebo arm (mean ±SD, 5.8±4.9 vs 2.5±3.9 mg/dL; p=0.029) and (133± 203 vs -30±37 μU /mM; p=0.045) respectively. Insulin sensitivity (S(I)) increased in the placebo arm compared to the CE/BZA treated subjects (1.8± 1.0 vs -0.7±1.8 (μU/mL) min(-1); p=0.029) without significant changes between treatment groups for AIRg, S(G) and DI. PAI-1 was decreased in the CE/BZA group compared to placebo (-2.5± 3.1 vs 1.3±2.9 ng/ml; p=0.088). Other inflammatory biomarkers were not significantly altered in any treatment group. Conclusions: A 12-week treatment of obese postmenopausal women with CE/BZA improves basal glucose concentration and beta-cell function during IVGTT without significant change in systemic inflammation. Sources of Research Support: NIH grants, Department of Veterans Affairs Merit Review Award, and Investigator-initiated award from Pfizer, Inc.