Improvement in Beta-Cell Function Observed After Three Years of BYETTA(R) (exenatide) Injection Therapy: Data Presented

ORLANDO, Florida, June 26, 2010 /PRNewswire/ --

-- Study Showed Improvements Compared to Insulin Glargine

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced results from a study comparing the effect of long-term treatment with either exenatide injection or insulin glargine on overall beta-cell function. (Beta cells are cells in the pancreas that produce insulin.) Three years of exenatide therapy improved indices of beta-cell function assessed four weeks after discontinuing therapy. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.

After three years of treatment, both therapies reduced HbA1c similarly (by 0.7 percentage points to 6.6 percent for exenatide and by 0.5 percentage points to 6.9 percent for insulin glargine). HbA1c is a measure of average blood sugar over three months. In addition, exenatide significantly reduced body weight compared to insulin glargine (7.7 kilogram difference between groups). After completion of three years of therapy, a four-week off-drug period followed to allow assessment of parameters of metabolic state including beta-cell function. Beta-cell function was assessed using a calculated disposition index (insulin secretion adjusted for insulin sensitivity). Exenatide increased insulin sensitivity by 39 percent and increased the disposition index, indicating an improvement in background beta-cell function. Insulin glargine had no effect on insulin sensitivity or disposition index.

"Type 2 diabetes is a progressive disease in which insulin production typically decreases over time," said Michaela Diamant, M.D., professor of diabetology, director, Diabetes Center VUMC, Amsterdam, the Netherlands, and principal investigator of the study. "These findings suggest that with extended use, exenatide treatment may help improve insulin production and help people with type 2 diabetes control their blood sugar levels."

Study Design and Findings

In the first portion of the study, metformin-treated patients with type 2 diabetes were randomized to receive exenatide (n=36) or insulin glargine (n=33) and measures of beta-cell function, blood sugar control and weight change were compared. Baseline characteristics were age 59 +/- years; HbA1c 7.5 +/- 0.8 percent; BMI 31 +/- 4 kg/m2; weight 91.6 +/- 13.1 kilograms. One-year study results, previously published in Diabetes Care, found that patients receiving exenatide, compared to those treated with insulin glargine, showed significant improvements in beta-cell function. However, the improvements were not sustained following an initial four-week off-drug period.

In this study, a total of 46 patients entered the two-year open-label extension period, and 36 completed the study (exenatide n=16; insulin glargine n=20). Insulin sensitivity and beta-cell function were assessed at baseline and after a second four-week off-drug period, following a total of three years of treatment. To assess beta-cell function, an estimate of insulin secretion (first-phase glucose stimulated C-peptide secretion) was measured. This measurement was adjusted for insulin sensitivity in the calculated disposition index. Both therapies reduced HbA1c similarly (to 6.6 +/- 0.2 percent and 6.9 +/- 0.2 percent for exenatide and insulin glargine, respectively) after three years of treatment. After the four-week off-drug period, the disposition index was increased in the exenatide-treated group compared to baseline (+1.43 +/- 0.78). The disposition index was reduced with insulin glargine (-0.99 +/- 0.65). In addition, exenatide increased insulin sensitivity by 39 percent, while insulin glargine treatment showed no effect. Thus, both insulin sensitivity and beta-cell function were improved after exenatide therapy for three years.

About Diabetes

It is estimated that by 2010, diabetes will affect 284.6 million adults worldwide and more than 55.4 million in Europe.(i, ii) Approximately 90 to 95 percent of those are affected by type 2 diabetes, a condition characterized by failure of the pancreatic beta-cell to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance.(iii)

Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.(iv) In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation as well as one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease).(v) In the European region, estimates indicate that at least 106 billion USD will be spent on healthcare for diabetes in 2010, accounting for 28 percent of global expenditure.(vi)

About exenatide Injection

Exenatide was the first approved incretin mimetic, a class of drugs for the treatment of type 2 diabetes. Exenatide exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar(vii). Exenatide is approved in the European Union as adjunctive therapy to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate glycaemic control on maximally tolerated doses of metformin and/or a sulfonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, more than one million patients worldwide have been treated with exenatide.

Important Safety Information for exenatide

In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulfonylurea, nausea (feeling sick), vomiting and diarrhea. For the full list of all side effects reported with exenatide, see the Package Leaflet. Exenatide should not be used in people who may be hypersensitive (allergic) to exenatide or any of the other ingredients.

About Amylin and Lilly

Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes, SYMLIN(R) (pramlintide acetate) injection and BYETTA(R) (exenatide) injection. Amylin's research and development activities leverage the Company's expertise in metabolism to develop potential therapies to treat diabetes and obesity. Amylin is headquartered in San Diego, California. Further information on Amylin Pharmaceuticals is available at www.amylin.com.

Through a long-standing commitment to diabetes care, Lilly seeks to provide patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been an industry leader in pioneering therapies to help healthcare professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients. For more information about Lilly's current diabetes products, visit www.lillydiabetes.com.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

(CONTINUA)