INEGY Better Than Lipitor™ In Achieving Recommended Levels Of LDL-Cholesterol In Diabetes 2 Patients With Hypercholesterolemia

Main Category: Diabetes
Also Included In: Cholesterol;  Statins
Article Date: 14 Jun 2007 - 1:00 PST

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INEGY™ (ezetimibe/simvastatin) was significantly more effective at influencing coronary heart disease (CHD) risk factors than Lipitor (atorvastatin) in type 2 diabetes patients with hypercholesterolemia according to results of two analyses presented at the European Atherosclerosis Society (EAS) meeting in Helsinki, Finland.1,2 Data showed that treatment with INEGY resulted in significantly more patients with type 2 diabetes reaching optional recommended levels of LDL ("bad") cholesterol (LDL-C) and achieved predefined values for apolipoprotein B (ApoB), non-HDL-cholesterol (non-HDL-C), compared to those treated with atorvastatin, at all doses investigated.1 In addition, INEGY also produced significantly greater reductions in a variety of lipoprotein and apolipoprotein ratios. 2

Type 2 diabetes is associated with a two- to fourfold increased risk for cardiovascular disease (CVD), 3 and one study showed that up to 80 percent of adult type 2 diabetic patients die from CVD.4 The risk of CVD in diabetes patients is so great that the NCEP ATP III* guidelines consider diabetes patients with no history of cardiovascular disease at equivalent risk to patients with diagnosed CHD.5,6 However, intensive lipid lowering therapy can be beneficial for diabetes patients and using the UKPDS risk engine model, it was calculated to contribute approximately 70 percent of the total calculated risk reduction in CVD events in a multi-factorial interventional study in type 2 diabetics with microalbuminuria.7,8

* NCEP ATP III is the U.S. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, a set of guidelines for effective patient identification, assessment, diagnosis, and treatment.

"A high proportion of people with type 2 diabetes also suffers from elevated cholesterol levels and are at high risk of developing coronary heart disease. Therefore, it is important that such patients reach their LDL-C goal as quickly and effectively as possible through aggressive lipid management in line with treatment guidelines by the Taskforce on Diabetes and Cardiovascular Diseases of the ESC and of the EASD, which recommend LDL-C goals of <70mg/dl for patients with type 2 diabetes and CVD," said Dr. Farnier, Point Medical Clinic, Dijon, France.

INEGY improved attainment of optional recommended levels of LDL-C and other CVD risk factors compared to atorvastatin in patients with type 2 diabetes and hypercholesterolemia

The first analysis was a post-hoc analysis based on data obtained from a multicenter, randomized, double-blind, six week parallel study in which the usual and alternate starting doses of INEGY (10/20 mg and 10/40 mg) and atorvastatin (10, 20, and 40 mg) were compared in patients with type 2 diabetes and hypercholesterolemia.1 The study assessed the proportion of type 2 diabetes patients treated with INEGY versus atorvastatin who attained LDL-C <70mg/dL with results showing that a significantly higher percentage of patients treated with INEGY compared to atorvastatin attained LDL-C <70 mg/dL at all dose comparisons1 (NCEP ATP III* guidelines recommend an LDL-C treatment goal of <100mg/dL patients with type 2 diabetes and hypercholesterolemia). Additionally a greater percentage of patients treated with INEGY achieved pre-specified target levels for LDL-C, ApoB, and non-HDL. At INEGY 10/20 mg, the percentage of patients who achieved hsCRP <2 mg/L was higher than with atorvastatin 10 or 20 mg.1 Based on these results, INEGY provides an important therapeutic option to type 2 diabetes patients for reaching treatment goals in the reduction of CVD risk.

INEGY more favorably influenced lipoprotein/apolipoprotein ratios in patients with type 2 diabetes and with LDL-C ≥100mg/dL than atorvastatin even when the atorvastatin dose was doubled

Results of the second analysis of the same randomized, double-blind, parallel-group trial involving 1,198 patients with type 2 diabetes with LDL-C ≥100mg/dL - showed that INEGY was significantly more effective at lowering LDL-C than atorvastatin at each dose comparison (ezetimibe/simvastatin 10/20 mg, 10/40 mg versus atorvastatin 10 mg, 20 mg and 40 mg; p<0.001).2 In addition, INEGY produced significantly greater reductions from baseline lipoprotein/apolipoprotein ratios (LDL-C:HDL-C, ApoB:ApoA-1, non-HDL-C:HDL-C and Total-C:HDL-C) compared to atorvastatin at all usual and alternative starting doses.2 The results showed that, through the inhibition of cholesterol absorption and production, INEGY had a more favorable effect on these selected lipoprotein/apolipoprotein ratios than atorvastatin, suggesting that it was more effective at reducing key markers of CHD risk.

Defining "inhibition of cholesterol absorption and production"

Cholesterol in the body originates from two main sources: absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues.10,11 Approximately two-thirds of intestinal cholesterol comes from biliary sources; only one third comes from dietary sources.9 Approximately 50 percent of cholesterol in the intestine is absorbed and re-circulated in the blood; the remainder is excreted.10

Cholesterol-lowering agents (statins) reduce cholesterol levels by inhibiting the production (synthesis) of cholesterol in the liver. INEGY™ contains the statin simvastatin, plus the active ingredient of EZETROL™ (ezetimibe), the first and only cholesterol absorption inhibitor which works by inhibiting intestinal absorption of cholesterol.

About INEGY™

INEGY™ has been developed and is being marketed by Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. (NYSE: MRK) and Schering-Plough Corporation (NYSE: SGP) in connection with a partnership formed by both companies to develop and market worldwide (excluding Japan) new prescription medicines in cholesterol management. Branded as INEGY™ in Europe, Middle East and Africa, the product is indicated (in the EU) as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia where use of a combination product is appropriate: 1) patients not appropriately controlled with a statin alone; and 2) patients already treated with a statin and ezetimibe. INEGY™ has an additional indication for homozygous familial hypercholesterolemia. It has been approved in more than 60 countries around the world including the United States, where the Food and Drug Administration approved it in 2004 - under the brand name VYTORIN - for the treatment of high LDL-C as adjuvant therapy to diet. The tolerability profile of INEGY™ is similar to simvastatin and atorvastatin, and is maintained over long-term therapy.

About Merck

Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., which operates in many countries as MSD (Merck Sharp & Dohme), is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com.

About Schering-Plough

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 33,500 people around the world. The company is based in Kenilworth, N.J., and its website is http://www.schering-plough.com.

Dyslipidemia: Incorrect balance of lipids in the bloodstream
Microalbuminuria: Leakage of small amounts of protein (albumin) into the urine and is an early warning of kidney damage
Vascular disease: Disease of the blood vessels

References:

1. Weinstock R et al. Effect of Ezetimibe/simvastatin versus Atorvastatin on Attaining Recommended levels of LDL-C, Apolipoprotein and B, non-HDL-C and hs-CRP in Type 2 diabetes - presented at the European Atherosclerosis Society congress (EAS) 2007, Helsinki, Finland.
2. Guyton J et al. Ezetimibe/simvastatin More Favorably Influences Lipoprotein/Apolipoprotein Ratios than Atorvastatin Monotherapy in Patients with Type 2 Diabetes - presented at the European Atherosclerosis Society congress (EAS) 2007, Helsinki, Finland.
3. American Diabetes Association. Dyslipidemia management in adults with diabetes. Diabetes Care 2004;27(Suppl. 1): S68-S71.
4. Laakso M, Lehto S. Epidemiology of macrovascular disease in diabetes, Diabetes Reviews. 1997;5:294-315
5. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Executive Summary of the 3rd Report of the National Cholesterol Education Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285: 2486-2497, 2001
6. Grundy S, et al. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III, GuidelinesArteriosclerosis, Thrombosis & Vascular Biology. 24(8):e149-e161, August 2004
7. Gaede, P, Pedersen O. Intensive, Integrated Therapy of Type 2 Diabetes Implications for Long-Term Prognosis, Diabetes. 2004;53(Suppl 3):S39-S47.
8. Stevens RJ et al. The UKOPDS Risk Engine: A Model for the Risk of Coronary Heart Disease in Type 2 Diabetes (UKPDS 56), Clinical Science. 2001;101,671-679
9. Ridker P, Haughie P. Prospective studies of C-reactive protein as a risk factor for cardiovascular disease. J Investig Med. 1998;46:391-395
10. Wilson MD, Rudel LL. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res 1994; 35:943-955.
11. Clearfield MD. A novel therapeutic approach to dyslipidemia. J Am Osteopath Assoc 2003; 102 (suppl-1): S16-S20.

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