By: Mohamed Dungersi
On January 27, the FDA approved Bydureon® (exenatide extended-release) for use in Type 2 Diabetes Mellitus (T2DM), as an adjunct to diet and exercise. Bydureon®, a product of Amylin Pharmaceuticals, is a modified formulation of the twice-daily injection, Byetta® (exenatide). It is the first once-a-week medication for T2DM in the market.
The twice-daily injection formulation, Byetta®, is also a recent addition to medications that used to control T2DM. The active ingredient, exenatide, was the first incretin mimetic used to treat T2DM. It is a GLP-1 (glucagon-like peptide-1) receptor agonist suggested to have multiple actions, such as the potentiation of glucose-mediated insulin secretion, suppression of postprandial glucagon release (via unknown mechanisms), slowed gastric emptying, and a central loss of appetite. All these actions, in combination, lead to decreased blood glucose levels and the control of T2DM. The effect of increased satiety, through delayed gastric emptying and a central loss of appetite, produces anorexia and weight loss. These are key components in treating the typical T2DM patient with exenatide.
Since most of the anti-diabetic agents cause weight gain as an undesirable consequence (as with pioglitazone), the use of incretins has been quickly gaining popularity. Victoza® (liraglutide), a once a day injection, is another incretin mimetic that was approved in January of 2010 for similar uses.
Bydureon® provides all the advantages of the incretin mimetics, but offers a much more convenient once-a-week dosing regimen. Although the FDA approved its use, there are still some safety concerns. The FDA is requesting the manufacturer to conduct a randomized, double blind, placebo-controlled trial evaluating the drug’s effect on the incidence of major cardiovascular events among patients with T2DM. The trial must also assess the risk other adverse events, such as pancreatic cancer, renal disorders, and serious hypoglycemia, as well as the long-term effects on potential biomarkers of medullary thyroid carcinoma (MTC). In addition, the company must conduct a number of studies with mice — and one that also includes mouse, rat, and human thyroid C cells — that focus on MTC. Bydureon® has a black box warning for MTC due to the incidence of thyroid C-cell tumors at clinically relevant exposures in rats. There is no established data on the incidence of such tumors or MTC in humans. Hence, patients with a personal or family history of MTC or patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should not use Bydureon®.
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