Amylin Pharmaceuticals, Inc., and Eli Lilly and Company announced that results from a Phase 3 open-label study of exenatide, the first in a new class of therapies for the treatment of type 2 diabetes known as Incretin Mimetics, showed that 44 per cent of the participants who completed 24 weeks of treatment achieved glucose level averages within the American Diabetes Association's (ADA) target range.
The findings from the ongoing study were presented at the 18th Congress of the International Diabetes Federation (IDF), Paris, France. These results are consistent with the 20-week results from the same open label study, which were presented in June at the ADA's 63rd Scientific Sessions in New Orleans, USA. These data are also consistent with a preliminary analysis of the first of three pivotal Phase 3 studies released August 6 by Amylin and Lilly, which showed a statistically significant reduction in glucose levels and body weight among exenatide users, when compared to placebo.
In the open-label data released today at IDF, exenatide was added to the treatment regimens of 155 patients who had failed to reach target glucose levels on metformin, sulfonylurea, or a combination of the two. Prior to adding exenatide, the average A1C, an average measure of glucose over three months, was 8.6 per cent. In the 105 patients who completed 24 weeks of treatment, the average A1C dropped 1.3 points to 7.3 per cent, nearing the ADA recommended target. In addition, participants' fasting glucose levels decreased from a pre-study baseline of 11.6 mmol/l (209 mg/dl) to 10.0 mmol/l (181 mg/dl) after 24 weeks. Patients completing 24 weeks lost on average 3.4 kilograms (7.5 pounds)."These results are important, because many patients with type 2 diabetes do not meet treatment targets. Those that do have difficulty maintaining those targets. The fact that many of the patients who failed to meet targets on other medications were successful in reaching target on exenatide is very encouraging," said Dr. Michael Nauck, Head of the Diabetes Center, Bad Lauterberg, Germany. "The closer patients stay to the target range, the more likely they are to avoid the devastating complications that often result from diabetes."
The findings from this open-label study are based on results from 105 patients who have been using exenatide for 24 weeks. These patients had been taking metformin, sulfonylureas or the combination of both metformin and sulfonylureas for at least three months prior to entering the study and had A1Cs between 7.5 and 12.0 per cent.
Researchers added twice-daily injections of exenatide to the patients' pre-study medication regimen, with an initial dose of 5 micrograms administered at breakfast and dinner, which was increased to 10 micrograms after four weeks. The most frequently reported adverse event was mild to moderate nausea, which decreased with continued treatment. Consistent with previous trials, mild to moderate hypoglycemia was most frequently observed in patients taking sulfonylureas. Some emesis was also observed. Of the 105 subjects included in the 24-week analysis, the overall dropout rate was approximately 12.5 per cent (n=15). Antibody formation was observed, however, the data do not demonstrate a relationship between antibody formation and exenatide's sustained effect on A1C.The effects on glucose control seen with exenatide treatment are likely due to several actions that are similar to those of the naturally occurring incretin hormone GLP-1.
These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood glucose, inhibiting the release of glucagon following meals and slowing the rate at which nutrients are absorbed into the bloodstream. (1) In animal studies exenatide administration resulted in preservation and formation of new beta cells, (2) the insulin-producing cells in the pancreas, which fail as type 2 diabetes progresses. Additional Exenatide Research Results Presented at IDFExenatide Long-Acting-Release (LAR) Data from a separate abstract presented at the IDF indicate that exenatide, when given in an extended-release formulation, continues to demonstrate a potent glucose-lowering effect as measured by A1C and fasting glucose levels in rats. An Investigational New Drug Application was submitted to the Food and Drug Administration (FDA) in March 2003 to support an independent program for exenatide LAR. The goal of the exenatide LAR program is to develop an extended-release, subcutaneous injection of exenatide, which could lead to weekly or monthly, rather than daily injections.
An animal study presented at the conference examined the impact of exenatide on beta cell function and mass. These study results indicate that exenatide preserves beta cell mass and stimulates beta cell neogenesis through a mechanism of action that is independent of the potential benefits gained from the compound's effect on weight loss and glucose control.
An estimated 194 million people around the world have diabetes, up from 135 million in 1995. (3) It is projected that 333 million people will have diabetes by the year 2025. In developing countries, the disease rate is expected to grow 170%, from 84 million to 228 million in 2025. (4) Approximately 90-95 per cent of those affected have type 2 diabetes, in which either the body does not produce enough insulin or the cells in the body do not respond normally to the insulin. According to the US Center for Disease Control's National Health and Examination Survey, 57 per cent of diabetes patients do not achieve target A1C levels with their current treatment regimen and approximately 41 per cent have A1Cs above 8 per cent. According to the ADA, patients with A1Cs above target are more likely to develop diabetes-related complications, such as kidney disease, blindness and heart disease.