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Exenatide Improves Beta-Cell Function Compared with Insulin Glargine

Posted: Wednesday, June 03, 2009

Over a 1-year period, treatment with exenatide improved beta-cell function significantly more, and led to greater weight loss, than did insulin glargine, in a study of patients with Type 2 diabetes who had previously been treated with metformin.

The two therapies reduced A1c levels by comparable amounts. After cessation of treatment, beta-cell function and glycemic control reverted to pretreatment levels among patients in both groups.

Dr. Michaela Diamant of the Free University Medical Center, Amsterdam, stated that this was the first study to compare "the effects of exenatide and insulin glargine on several aspects of beta-cell function in human (Type 2 diabetes), as measured by a gold-standard method," in this case a hyperglycemic clamp.

The study was conducted between September 2004 and September 2007 at three centers in northern Europe. Sixty-nine patients, all of whom had been receiving metformin treatment at a stable dose, were randomized to receive exenatide (a glucagon-like peptide-1 receptor agonist) or insulin glargine.

Sixty patients completed the 52-week treatment period. Both groups achieved a mean A1c of 6.8% at 52 weeks. Patients receiving exenatide lost an average of 3.6 kg, while those receiving insulin glargine lost an average of 1.0 kg (P < 0.0001). During a 12-week off-drug period following the 52 weeks, both groups' average body weight trended toward baseline values, though the exenatide group regressed less (p = 0.03).

Both drugs improved insulin sensitivity to approximately the same extent, although 4 weeks after discontinuation insulin sensitivity remained significantly better in the exenatide group than in the insulin glargine group. The report notes that a 2-year extension of this study is under way, to study a possible preserving effect of exenatide on beta-cell function.

As measured by hyperglycemic clamp, beta-cell function in the exenatide group improved significantly, and significantly more than in the insulin glargine group, after 52 weeks. After 4 weeks of discontinuation, however, beta-cell function returned to baseline levels in both groups, with accompanying increases in plasma glucose and A1c.

The most common adverse event in the exenatide-treated patients, seen in half of them, was mild to moderate nausea.

Source: Diabetes In Control: Diabetes Care May;32:762-768.