Aim: The ability of the incretin mimetic exenatide to improve glycaemic control and reduce body weight was assessed over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with maximally effective doses of metformin. Methods: In this interim 82-week analysis, 150 (total cohort) of an eligible population of 183 patients opted to continue exenatide treatment in an uncontrolled open-label extension of a 30-week double-blind, placebo-controlled trial. Of these, 92 patients (completer cohort) achieved 82 weeks of exenatide therapy. Patients continued metformin throughout the study. Results: At the end of the placebo-controlled trial, exenatide resulted in an haemoglobin A1c (HbA 1c ) reduction from baseline of À1.0 AE 0.1% (mean AE SE) (exenatide treatment arms), with durable HbA 1c reductions after 82 weeks of À1.3 AE 0.1%. The percent of patients who achieved HbA 1c 7% at weeks 30 and 82 was 46 and 59% respectively. After 30 weeks, exenatide caused a reduction in weight from baseline of À3.0 AE 0.6 kg, with a progressive reduction in weight of À5.3 AE 0.8 kg after 82 weeks. In addition, exenatide treatment produced clinically significant improvements in cardiovascular risk factors after 82 weeks. The most frequent adverse event after 30 and 82 weeks of exenatide was nausea, which was generally of mild-or-moderate intensity. It decreased in incidence after initiation in the controlled trial and the uncontrolled open-label extension. Hypoglycaemia was rare, with no severe events. Conclusion: Exenatide was generally well tolerated, producing a durable reduction in HbA 1c and a progressive reduction in weight over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with metformin.

These results support the need for a prospective, randomized, controlled study of BP changes during exenatide treatment in patients with hypertension and type 2 diabetes.

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These data demonstrate a positive relationship between baseline HbA(1c) and the magnitude of HbA(1c) change across 10 categories of glucose-lowering therapies, irrespective of class or mode of action. These observations should be considered when assessing clinical efficacy of diabetes therapies derived from clinical trials.

Rabbit polyclonal antibodies were raised to rat Kir2.0 (Kir2.1, Kir2.2 and Kir2.3) inwardly rectifying potassium ion channel proteins. The antibody specificities were confirmed by immunoprecipitation of [35S]-methionine-labelled in vitro translated channel proteins and western blotting. Immunohistochemistry revealed a different patterns of expression of Kir2.0 subfamily proteins in the rat hind-brain (cerebellum and medulla) and fore-brain (hippocampus). Notably, only Kir2.2 protein was detected in the cerebellum and medulla, Kir2.1, Kir2.2 and Kir2.3 proteins were expressed in the hippocampus and immunostaining was not limited to neuronal cell types. Anti-Kir2.1 (fore-brain only) and anti-Kir2.2 (fore- and hind-brain) antibodies showed positive staining in macroglia, endothelia, ependyma and vascular smooth muscle cells. In contrast, anti-Kir2.3 (fore-brain only) immunostaining was limited to neurons, macroglia and vascular smooth muscle. These results indicate that specific regions within the rat fore- and hind-brain have differential distributions of inwardly rectifying potassium ion channel proteins.