ROME, September 9 /PRNewswire/ --
- Patients Taking Exenatide Also Reduced Food Intake
Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced results from a randomized, double-blind, cross-over, four-week head-to-head study demonstrating that BYETTA(R) (exenatide) injection, a GLP-1 receptor agonist, provided significantly lower glucose levels in the post-meal setting when compared to Januvia(TM) (sitagliptin), a DPP-4 inhibitor. Additionally, patients treated with exenatide reduced post-meal glucagon, showed more efficient use of their body's own insulin and decreased their food intake when compared to sitagliptin. This is the first reported head-to-head study directly comparing the therapeutic mechanisms of action (MOA) of exenatide and sitagliptin. The findings were presented at the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Rome, Italy. The study will also be published in the peer-reviewed journal, Current Medical Research and Opinion.
"There has been some confusion in the marketplace about the therapeutic differences between exenatide and sitagliptin, and data from this first head-to-head study showed a clear difference in the MOAs and resultant short-term clinical effects between these two agents. Exenatide works directly on the GLP-1 receptor, whereas sitagliptin indirectly affects GLP-1 levels," said Ralph DeFronzo, M.D., professor of medicine and chief of the diabetes division at the University of Texas Health Science Center in San Antonio and a clinical trial investigator on this study. "Patients on exenatide experienced significantly lower post-meal glucose levels, improved measures of beta cell function and decreased food intake."
The primary endpoint of this four-week study compared the effect of exenatide and sitagliptin on 2-hour post-meal glucose. Secondary endpoints included post-meal glucagon, insulin secretion rate, gastric emptying, and food intake. Patients were randomly assigned to treatment with either exenatide (5 mcg twice daily for the first week followed by 10 mcg twice daily for the second week) or sitagliptin (100 mg once daily) for two weeks; patients were then switched to the alternate therapy for the remaining two weeks. At baseline and at the end of each two week treatment period, patients underwent a standard meal test and other evaluations to assess each drug's effects on various measures of post-meal glucose control, indicators of beta cell function and other parameters.
In response to a standard meal, patients (evaluable population, N=61) treated with exenatide had significantly improved post-meal glucose levels two hours after the standard meal when compared to sitagliptin (7.4 mmol/L vs. 11.5 mmol/L at 2 hours respectively, baseline: 13.6 mmol/L; P<0.0001). Differences in post-meal glucose levels for the intent-to-treat (ITT) population (N=95) also showed significantly lower post-meal glucose levels with exenatide compared to sitagliptin (9.2 mmol/L vs. 11.7 mmol/L; P<0.0001). As patients were switched from sitagliptin to exenatide after two weeks, the post-meal glucose was further improved (-4.22 mmol/L), while patients who switched from exenatide to sitagliptin partially lost the post-meal glucose (+4.05 mmol/L) control achieved with exenatide.
The study also showed that after two weeks of treatment both exenatide and sitagliptin improved fasting plasma glucose (FPG) (-0.8 mmol/L and -1.1 mmol/L respectively, baseline: 9.9 mmol/L). Exenatide significantly improved an indicator of beta cell function, the insulinogenic index of insulin secretion, compared to sitagliptin (ratio: 1.50 +/- 0.26, P=0.0239). Exenatide reduced food intake compared to sitagliptin during buffet-style meals (-134 kcal vs. +130 kcal, P=0.0227), and patients treated with exenatide experienced a greater reduction in post-meal triglyceride concentrations compared to sitagliptin (ratio AUC: 0.90 +/- 0.04, P=0.0118).
The most common adverse events for both exenatide and sitagliptin were mild to moderate nausea (exenatide: 34 percent vs. sitagliptin: 12 percent) and vomiting (exenatide: 24 percent vs. sitagliptin: 3 percent). There were no major hypoglycaemic events; a single event of minor hypoglycaemia (moderate intensity) was reported in a patient treated with exenatide.
About BYETTA(R) (exenatide) Injection
Exenatide is the first and only 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.(i) 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 sulphonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, approximately one million patients worldwide have been treated with exenatide.
Diabetes affects an estimated 246 million adults worldwide and more than 48 million in Europe.(ii,iii) 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.(iv) In western countries, around 90 percent of type 2 diabetes cases are attributable to weight gain.(v)
Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.(vi) In virtually every developed society, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation, as well as death through its effects on cardiovascular disease (70-80 percent of people with diabetes die of cardiovascular disease).(vii) The total cost of caring for people with diabetes in Europe is estimated between 28 billion and 53 billion Euros per year. The calculated estimates of the costs of diabetes care in Europe amount to 42.8 billion International Dollars per year.(viii)
Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulphonylurea, 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 Incretin Mimetics
Incretin mimetics are a distinct class of agents used to treat type 2 diabetes. An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of the naturally occurring human incretin hormone GLP-1. These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake.
About Amylin and Lilly
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. 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 with over 2,000 employees in the United States.
Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the 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.
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs.
This press release contains forward-looking statements about Amylin and Lilly. Actual results could differ materially from those discussed or implied in this press release due to a number of risks and uncertainties, including the risk that exenatide and the revenues generated from exenatide may be affected by competition; unexpected new data; safety and technical issues; clinical trials not confirming previous results; pre-clinical trials not predicting future results; new drug applications and label expansion requests not being submitted in a timely manner or receiving regulatory approval; or manufacturing and supply issues. The potential for exenatide may also be affected by government and commercial reimbursement and pricing decisions, the pace of market acceptance, or scientific, regulatory and other issues and risks inherent in the commercialization of pharmaceutical products. These and additional risks and uncertainties are described more fully in Amylin's and Lilly's most recent SEC filings including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin and Lilly undertake no duty to update these forward-looking statements.
Presentation Number: 872
i Kolterman, O, Buse J, Fineman M, Gaines E, Heintz S, Bicsak T, Taylor K, Kim D, Aisporna M, Wang Y, Baron A. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting glucose in subjects with type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 2003; 88(7):3082-3089.
ii The International Diabetes Federation Diabetes Atlas. Available at: http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC22682A. Accessed on May 22, 2008.
iii The International Diabetes Federation, Prevalence / All diabetes. Available at: http://www.eatlas.idf.org/Prevalence/All_diabetes/. Accessed on May 22, 2008.
iv Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999; 281 (21):2005-2012.
v The International Diabetes Federation Diabetes Atlas. Available at: http://www.eatlas.idf.org/Obesity_and_type_2_diabetes/. Accessed on May 22, 2008.
vi The International Diabetes Federation, Prevalence / All diabetes. Available at http://www.eatlas.idf.org/Prevalence/All_diabetes/. Accessed on May 22, 2008.
vii The International Diabetes Federation, Complications. Available at http://www.eatlas.idf.org/Complications/. Accessed on May 22, 2008.
viii The International Diabetes Federation, Diabetes Atlas, Second edition. Available at: http://www.eatlas.idf.org/Costs_of_diabetes/Calculated_cost_estimates/. Accessed August 26, 2008
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