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Fig. 6 (a) NF-κB activity in the subcutaneous abdominal adipose tissue (AT) at baseline (white bars) and after 12 weeks’ (black bars) treatment with salsalate or placebo. Data are means±SE; *p<0.05, week12 vs baseline; ††p<0.01, salsalate vs placebo; repeated measures
ANCOVA adjusted for site. (b) Spearman correlation between followup plasma salicylate levels and change (follow-up minus baseline) in adipose tissue NF-κB activity (r=−0.53, p=0.02). AU, arbitrary units
Ranolazine is a first-in-class antianginal agent with anti-ischemic effects that inhibits the cardiac late sodium current. Prior studies supported a HbA1c lowering effect by ranolazine in patients (pts) with chronic angina and T2DM (post hoc analysis of the CARISA study; total n=823, 23% DM pts), as well as in pts with DM, coronary artery disease (CAD), and acute coronary syndromes (pre-specified subset analysis of the MERLIN TIMI-36 study; total n=6560, 34% DM pts).
In this double-blind study, 80pts with HbA1c 7-11% (on non-insulin medical therapy) were randomized to placebo or ranolazine ER (1000mg BID) for 12 weeks. The effect of ranolazine on HbA1c, 2-hour postprandial glucose (PPG), and fasting serum glucose (FSG) was determined.
Mean baseline HbA1c was 8.5% and 8.4% for the placebo and ranolazine groups, respectively. Ranolazine significantly reduced placebo-corrected HbA1c by 0.53%, and the reduction was even greater in pts with higher baseline HbA1c levels. Ranolazine also reduced placebo-corrected PPG levels in all pts, with a 35.8mg/dL reduction in the PPG subgroup with baseline FSG>140mg/dL. Although not statistically significant, ranolazine also lowered FSG levels in all pts; a greater placebo-corrected reduction was observed in the FSG subgroup with baseline FSG>140mg/dL.
In summary, in T2DM pts, we confirm prior observations in pts with CAD and T2DM that ranolazine significantly improves HbA1c when added to existing non-insulin anti-DM therapy. Compared to FSG, greater placebo-corrected reductions in PPG were observed, particularly in the subset of pts with FSG>140mg/dL.
FOX 01: Forkhead box
CPT 1ª: Carnitine Palmitoyl Transferase 1ª
SIRT1: Silent Mating Type Information Regulation 1 homolog
PTPN1: Protein Tyrosine Phosphatase, Non-receptor type 1
FGF21: Fibroblast Growth Factor 21
IKKβ: Proteína Quimioatrayente de monocitos Beta
NFκβ: Nuclear Factor k Beta