Exenatide plus metformin compared to metformin alone on β-cell function in patients with Type 2 diabetes

Department of Internal Medicine and Therapeutics, University of Pavia, Pavia Metabolic Unit, Regional Hospital, Varese Ospedale Pesenti Fenaroli, Alzano Lombardo, Bergamo Hospital Centre of Diabetes, Sant'Angelo Lodigiano, Lodi RSA Villa Mafalda, Borgo San Siro, PAVIA Fondazione Ospedale della Carità, Casalbuttano, Cremona, Italy.
Diabetic Medicine (Impact Factor: 3.12). 04/2012; 29(12). DOI: 10.1111/j.1464-5491.2012.03699.x
Source: PubMed


Diabet. Med. 29, 1515–1523 (2012)
Aim To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone.
Methods A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation.
Results Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.
Conclusion Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.

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    • "Considering that diabetes per se is a risk factor for acute pancreatitis, it is not yet established whether exenatide can induce this serious adverse event (Ahrén, 2011). Exenatide significantly improves glycaemic control and shows greater decrease in body weight if used in combination with metformin (Derosa et al., 2012). Exenatide long-acting formulation Ex(OW) results in greater improvements in glycemic control compared with regular exenatide, but shows lower HbA1c reductions compared with liraglutide once daily (DURATION program) (J.B. "
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    Life sciences 01/2014; 99(1). DOI:10.1016/j.lfs.2013.12.210 · 2.70 Impact Factor
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    • "The observed 28% improvement in disposition index is consistent with this observation. Comparatively, studies in diabetic adults (who are likely to have an exaggerated response to therapy) have shown that mainstream medications affecting only β-cell secretion capacity have achieved improvements of 55% (dipeptidyl peptidase-4 antagonists) [25] and 100% (glucagon-like peptide-1 agonists) [26]. Hence, compared to these drugs that only improve insulin secretion, OLE improves both insulin sensitivity and pancreatic β-cell secretory capacity. "
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