Happy Friday everyone. Resverlogix will present a poster on Sunday at the American Diabetes Association meeting. The abstract was released on May 29th. I previously posted message for the poster title, but here is the link to the poster abstract. If that fails, I've copied the poster text here too:

1189-P - Effects of the ApoA-I Inducer RVX-208 on Glucose Metabolism in Individuals with Prediabetes

Authors

ANDREW L. SIEBEL, MELISSA F. FORMOSA, ALAINA K. NATOLI, MEDINI REDDY-LUTHMOODOO, ANDREW L. CAREY, GERRIT VAN HALL, JIM D. OTVOS, KERRY-ANNE RYE, JAN JOHANSSON, ALLAN GORDON, NORMAN WONG, PHILIP BARTER, STEPHEN J. DUFFY, BRONWYN A. KINGWELL, Melbourne, Australia, Copenhagen, Denmark, Raleigh, NC, Sydney, Australia, Calgary, AB, Canada

Disclosures

A.L. Siebel: None. M.F. Formosa: None. A.K. Natoli: None. M. Reddy-Luthmoodoo: None. A.L. Carey: None. G. van Hall: None. J.D. Otvos: Employee; Author; LipoScience. K. Rye: None. J. Johansson: Employee; Author; Resverlogix Corp. A. Gordon: Employee; Author; Resverlogix Corp. N. Wong: Employee; Author; Resverlogix Corp. P. Barter: Consultant; Author; Resverlogix Corp. S.J. Duffy: Research Support; Author; Resverlogix Corp. B.A. Kingwell: Research Support; Author; Resverlogix Corp.

High-density lipoprotein (HDL) and its major apolipoprotein, apoA-I modulate glucose metabolism through multiple mechanisms.1,2 This study determined the effects of the putative apoA-I inducer, RVX-208 on glucose metabolism in individuals with prediabetes.

Twenty unmedicated males with prediabetes received 100mg b.i.d RVX-208 and placebo each for 29-33 days separated by a wash-out period of 21-35 days in a randomised, cross-over design. Plasma HDL-cholesterol and apoA-I were assessed as well as lipoprotein particle size using nuclear magnetic resonance (NMR) spectroscopy. A modified frequently sampled OGTT (fsOGTT) protocol with both oral ([U-13C]D-glucose) and infused ([6,6-2H2]D-glucose and [1,1,2,3,3-D5]glycerol) stable isotope tracers was employed to assess postprandial plasma glucose, indices of insulin secretion and insulin sensitivity, glucose kinetics and lipolysis.

RVX-208 did not change plasma HDL-cholesterol or apoA-I concentration, but increased the concentration of medium-sized HDL particles and decreased both intermediate-density lipoprotein (IDL) particle and small-sized HDL particle concentration (all p<0.05). In response to a glucose load, after RVX-208, plasma glucose concentration peaked at a similar level to placebo, but 30min later and the elevation was more sustained (treatment effect, p=0.002). There was a reduction and delay in total (p=0.001) and oral (p=0.003) glucose rate of appearance in plasma and suppression of endogenous glucose production (p=0.014) after RVX-208 treatment. The rate of glucose disappearance was also lower following RVX-208 (p=0.016), but there was no effect on glucose oxidation.

The effects of RVX-208 on oral glucose absorption and endogenous glucose production have potential implications for long term glycemic control.

1. Drew, et al. Circulation 119, 2103-2111 (2009).

2. Drew, et al. Nat Rev Endocrinol 8, 237-245 (2012).