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

Abstract

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 β-cell function and/or insulin sensitivity and their combined product. Research design and methods Thirty-three patients with type 2 diabetes were investigated. Their β-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 1c and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA 1c 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 β-cell function rather than increased insulin sensitivity accounts for the bulk of HbA 1c reduction following 6 months of exenatide treatment.