Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity

Objective. This study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of beta-cell function and/or insulin sensitivity and their combined product. Research design and methods. Thirty-three patients with type 2 diabetes were investigated. Their beta-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA(lc), and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA(lc) response. Results. After 6 months, unadjusted HOMA-B increased from 33 +/- 24% to 43 +/- 23% (P=0.0210), whereas there was no significant change in HOMA-S (from 58 +/- 35% to 61 40%). The hyperbolic product increased by a relative 70% (from 15 +/- 7% to 22 +/- 15%; P=0.0055). Body mass index decreased from 32.2 +/- 5.1 kg/m(2) to 31.0 +/- 4.8 kg/m(2) (P<0.0001) and HbA(1c) from 8.8 +/- 1.0% to 7.6 +/- 1.2% (P<0.0001). No change was observed in adiponectin concentrations. Higher baseline HbA(1c) values were a significant predictor of therapeutic response. Conclusion. - Exenatide significantly increased HOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved beta-cell function rather than increased insulin sensitivity accounts for the bulk of HbA(1c) reduction following 6 months of exenatide treatment. (C) 2010 Elsevier Masson SAS. All rights reserved.