1.
Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole.
Bell, LN, Nguyen, AT, Li, L, Desta, Z, Henry, NL, Hayes, DF, Wolff, AC, Stearns, V, Storniolo, AM, Flockhart, DA, et al
Journal of clinical pharmacology. 2012;(12):1852-60
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Abstract
Effects of aromatase inhibitor (AI) therapy on the plasma lipid profile are not clear. Here the authors describe changes in fasting lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides) before and after 3 months of exemestane or letrozole treatment. HDL was reduced in the entire cohort (P < .001) and in the exemestane group (P < .001) but unchanged in the letrozole group (P = .169). LDL was increased in the entire cohort (P = .005) and in the letrozole group (P = .002) but unchanged in the exemestane group (P = .361). This effect was at least partially attributable to washout of tamoxifen as only patients with prior use of tamoxifen experienced a significant increase in LDL. Baseline HDL was an independent predictor of the change in HDL (r(2) = -0.128, P < .001), and prior tamoxifen use was associated with greater increases in LDL (r(2) = 0.057, P < .001). Use of lipid-altering medications did not protect against the exemestane-induced drop in HDL or the increase in LDL observed in women with prior use of tamoxifen taking letrozole. In conclusion, AI treatment and/or washout of tamoxifen induced detrimental changes in the lipid profile of postmenopausal women with breast cancer.
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Effects of sitagliptin on 24-h glycemic changes in Japanese patients with type 2 diabetes assessed using continuous glucose monitoring.
Mori, Y, Taniguchi, Y, Matsuura, K, Sezaki, K, Yokoyama, J, Utsunomiya, K
Diabetes technology & therapeutics. 2011;(7):699-703
Abstract
BACKGROUND This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes. SUBJECTS AND METHODS The study was a prospective open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug. CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration. The average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, mean amplitude of glycemic excursions (MAGE), and hyperglycemic and hypoglycemic time periods were compared before and after administration. RESULTS Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, MAGE, and hyperglycemic time, compared with these parameters before administration. There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration. CONCLUSIONS Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation, including postprandial hyperglycemia.
3.
Sitagliptin treatment of patients with type 2 diabetes does not affect CD4+ T-cell activation.
White, PC, Chamberlain-Shea, H, de la Morena, MT
Journal of diabetes and its complications. 2010;(3):209-13
Abstract
Dipeptidyl peptidase IV (DPP4) inhibitors have recently become widely used for treating type 2 diabetes, but in meta-analyses are associated with a mildly increased risk of all-cause infections. CD26 is a cell-surface form of DPP4 which can costimulate T-cell proliferation, raising the possibility that DPP4 inhibitors might adversely affect immune function. To address this issue in an observational study, two groups of 20 subjects each were recruited from a private endocrinology practice; one group consisted of type 2 diabetes patients treated for at least 6 months with the DPP4 inhibitor, sitagliptin, whereas patients in the other group had never been treated with this agent. The groups were similar with regard to sex and racial composition, body mass index, hemoglobin A(1c), and use of other medications for diabetes, but the sitagliptin group was slightly older. A blood sample from each patient was analyzed for CD4+ T-cell activation in response to phytohemagglutinin using adenosine triphosphate (ATP)-stimulated bioluminescence. There was not a significant difference in T-cell activation between the treatment groups (median, 419 and 481 ng/ml ATP in the groups that were and were not treated with sitagliptin, respectively). Thus the observed increased rate of infection in diabetic patients treated with sitagliptin cannot be explained by a major effect on T-cell activation. Randomized studies, preferably using several assays of immune function, should be performed to confirm and extend these findings.