Aims: Our aim was to explore predictive factors for the pleiotropic responses to exenatide during the first 12 weeks of therapy, and associations between these responses.
Methods: This was an observational study based on patients (n=83) with type 2 diabetes mellitus (T2D) in whom exenatide had been added to existing oral hypoglycaemic therapy. Exenatide was administered subcutaneously (5 mcg bd for the first month, 10 mcg bd thereafter). Data collected (at baseline and following up to 12 weeks of exenatide therapy) included weight, waist circumference (WC), HbA1c, fasting lipid profile and blood pressure (BP). Analyses included paired-sample t-tests and Pearson correlations. Data are shown as mean (S.D.) at baseline and following exenatide therapy respectively.
Results: Duration of exenatide therapy (n=83) was 312 weeks (mean 7 weeks (S.D. 3.5)). Following early exenatide therapy, there were significant reductions in weight (112.3 kg (20.4) versus 108.7 kg (19.3), P=5.1×10−10), WC (125.7 cm (16.2) versus 121.6 cm (13.2), P=3.9×10−4), HbA1c (9.5% (1.4) versus 8.9% (1.8), P=0.03) and systolic BP (139 mmHg (13) versus 133 mmHg (16), P=0.03). There were no significant changes in fasting lipid profile or diastolic BP. In separate multivariate analyses using total weight loss and reduction in HbA1c as dependent variables, initial weight (P=4.7×10−3) and initial HbA1c (P=3.3×10−3) were significant and independent variables respectively. Baseline weight correlated significantly with weight loss (r2=0.30, P=4.8×10−3), and baseline HbA1c with reduction in HbA1c (r2=0.47, P=1.2×10−3). Weight loss and reduction in HbA1c during exenatide therapy did not correlate with each other.
Conclusions: Baseline weight and HbA1c independently associate with early reduction in weight and HbA1c respectively, during treatment with exenatide therapy. Obese T2D patients with poor glycaemic control are most likely to derive early benefit from exenatide treatment, although weight reduction does not necessarily correlate with improved glycaemic control suggesting variable independent effects of exenatide on appetite and β-cell function between patients.