Physicians Call for Better Guidance on the use of Statins in Patients at High Risk of Developing Diabetes

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Kowa Company, Ltd.

14 Nov, 2012, 08:00 GMT

WOKINGHAM, England, November 14, 2012 /PRNewswire/ --

On World Diabetes Day, outputs from a consultation with physicians, including cardiologists and diabetologists, held during the World Congress on Prevention of Diabetes and its Complications (WCPD) in Madrid, has highlighted a requirement for improved guidance on how to treat cardiovascular disease risk in patients at risk of developing diabetes.[1]

This call for guidance has come in response to further evidence presented at the WCPD that demonstrates how statins differ in their effect on developing diabetes.[2],[3] In addition, consulted physicians noted that recent warnings about the potential for statins to cause diabetes in certain patients were causing other treating physicians to be more cautious about prescribing these lipid-lowering drugs.[1]

"Although no-one doubts the huge benefit of statins in reducing cardiovascular disease," said Prof Kausik Ray, Professor of Cardiovascular Disease Prevention, St George's, University of London, "these insights demonstrate how the medical community is taking the diabetogenic risk of statins seriously and highlight the need for further research and guidance in how to treat patients with high cholesterol who are at risk of developing diabetes."

Although statins are considered safe and well-tolerated,[4] conflicting data exist regarding the effects of some statins on the risk of developing diabetes. The largest meta-analysis of these data included 13 trials with a total of 91,140 participants and concluded that statin therapy is associated with a 9% increased risk of new-onset diabetes.[5] These studies resulted in a change made to the labels of some statins to include a warning of this risk.

Mechanisms explaining the potentially higher incidence of diabetes with statin therapy have not yet been identified and studies looking at statins' effect on glucose metabolism suggest that the effect may differ between statins. There are a number of markers that can be used to measure impacts on glucose metabolism such as increased fasting plasma glucose and HbA1c in the blood. Some statins (e.g. atorvastatin) have been associated with increased HbA1c levels in patients receiving intensive, but not moderate, therapy.[6],[7] Other statins (e.g. pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without diabetes or metabolic syndrome.[8]-[16]

New data presented during the WCPD demonstrated that both pitavastatin and pravastatin have no effect on fasting plasma glucose over 12 weeks in elderly patients[2] and over 6 months in a group of patients with carefully defined metabolic syndrome who have multiple risk factors for diabetes.[3] These data add to the building body of evidence suggesting pitavastatin has a positive effect on glucose metabolism and hence may not carry the same risk of developing diabetes as other statins.[8],[10]-[13] The J-PREDICT trial, currently being undertaken in Japan, will aim to clarify these data by evaluating the effect of pitavastatin on the risk for diabetes in more than 1,200 people with impaired glucose tolerance.[17] This study is due to finish in 2015.

About the consultation

The consultation was conducted at the KOWA sponsored satellite symposium held during the World Congress on Prevention of Diabetes and its Complications (WCPD) from 11-14 November 2012 in Madrid, Spain.

About LIVAZO®

LIVAZO® (pitavastatin) is a HMG-CoA reductase inhibitor indicated for patients with primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated TC, LDL-C, Apo B, TG, and to increase HDL-C. LIVAZO® is predominantly metabolized via glucuronidation and is only minimally metabolised by CYP system, which may help reduce its potential for CYP-mediated drug-drug interactions.

LIVAZO®, also known as LIVALO® and ALIPZA® in some markets, has been available in Spain, Portugal and Lebanon since 2011 and is available in the US (2010), Mexico (2012), Japan (2003), South Korea (2005), Thailand (2008), China (2009), Indonesia (2012) and Taiwan (2012).

In much of Europe, pitavastatin will be marketed by Recordati as LIVAZO®. Pitavastatin is available in three dosage strengths (1mg, 2mg and 4mg).[18] For more information about the geographical availability of pitavastatin and marketing companies please visit the Kowa Pharmaceutical Europe website www.kowapharmaceuticals.eu

About Kowa

Kowa Company, Ltd. (KCL) is a privately held multinational company headquartered in Nagoya, Japan. Established in 1894, KCL is actively engaged in various business fields with major focuses on the manufacturing and sales of pharmaceutical products, LED lighting equipment and green products, and the trading of textile goods, machinery, building materials and chemical products. KCL's pharmaceutical division was founded in 1947, and is focused on cardiovascular therapeutics, with sales of the company's flagship product, pitavastatin (known as LIVALO®, LIVAZO® and ALIPZA® in different markets) totalling €500 million (approximately 16% market share) in Japan during 2011 fiscal year.

Kowa Research Europe Ltd. (KRE), established in 1999 in the United Kingdom, is responsible for European clinical trials for Kowa's strategic global pharmaceutical development.

Kowa Pharmaceutical Europe (KPE) Co. Ltd, established in 2000, is a specialty pharmaceutical company located in Wokingham, UK, focused primarily on cardiometabolic therapeutics. Working in harmony with KRE, these European pharmaceutical divisions of Japanese Kowa Company, Ltd. are committed to ground-breaking research, development and marketing to ensure quality products are made available to people around the world, enabling them to enjoy a better standard of health and a more comfortable life.

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References

  1. Kowa data on file. Report from consultation at the KOWA sponsored satellite symposium held during the World Congress on Prevention of Diabetes and its Complications (WCPD) from 11-14 November 2012 in Madrid, Spain.  
  2. Sponseller CA, Stender S, Zhu B, et al. Neutral effects of pitavastatin and pravastatin on fasting plasma glucose over 12 weeks in elderly patients with primary hyperlipidemia or mixed lipidemia. Abstract 2421526. Presented at the 7th World Congress on Prevention of Diabetes and its Complications 2012. Madrid, Spain.
  3. Hounslow N, Robillard P, Suzuki M, et al. Pitavastatin is without effect on glycaemic parameters in metabolic syndrome. Abstract 7161542. Presented at the 7th World Congress on Prevention of Diabetes and its Complications 2012. Madrid, Spain.
  4. Armitage J. The safety of statins in clinical practice. Lancet. 2007;370:1781-90.
  5. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
  6. Koh KK, Quon MJ, Han SH, et al. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol 2010;55:1209-1216.
  7. Sabatine MS, Wiviott SD, Morrow DA, et al. High-dose atorvastatin associated with worse glycemic control: a PROVE-IT TIMI 22 substudy. Circ. 2004;110(Suppl 3):834.
  8. Yamakawa T, Takano T, Tanaka S, et al. Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus. J Atheroscler Thromb. 2008;15:269-275.
  9. Yokote K, Saito Y. Influence of statins on glucose tolerance in patients with type 2 diabetes mellitus: subanalysis of the collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study). J Atheroscler Thromb. 2009;16:297-298.
  10. Teramoto T, Urashima M, Shimano H, et al. A large-scale study on cardio-cerebrovascular events during pitavastatin (LIVALO tablet) therapy in Japanese patients with hypercholesterolemia LIVES 5-year extension study. Jpn Pharmacol Ther. 2011;39:789-803.
  11. Teramoto T, Shimano H, Yokote K, Urashima M. New evidence on pitavastatin: efficacy and safety in clinical studies. Expert Opin Pharmacother. 2010;11:817-828.
  12. Saku K, Zhang B, Noda K, et al. Randomized head-to-head comparison of pitavastatin, atorvastatin and rosuvastatin for safety and efficacy - The PATROL study. Circ J. 2011;75(6):1493-505.
  13. Kryzhanovski V, Morgan R, Sponseller C et al. Pitavastatin 4mg provides significantly greater reduction in LDL-C compared to pravastatin 40mg with neutral effects on glucose metabolism: prespecified safety analysis from the short-term phase 4 prevail UK trial in patients with primary hyperlipidemia or mixed dyslipidemia. JACC. 2012;59:E1692
  14. Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2010;87(1):98-107.
  15. Gumprecht J, Gosho M, Budinski D, Hounslow N. Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20-40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia. Diabetes Obes Metab. 2011;13(11):1047-55.
  16. Kryzhanovski V, Eriksson M, Hounslow N and Sponseller C. Short-term and long-term effects of pitavastatin and simvastatin on fasting plasma glucose in patients with primary hyperlipidemia or mixed dyslipidemia and >2 risk factors for coronary heart disease. J Am Coll Cardiol. 2012;59(13s1):E1659.
  17. Yamazaki T, Kishimoto J, Ito C et al. Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (the J-PREDICT study): rationale, study design, and clinical characteristics of 1269 patients. Diabetol Int. 2011;2:134-40.
  18. Pitavastatin Summary of Product Characteristics. Available at http://www.kowapharmaceuticals.eu/_client/pdfs/livazo_smpc.pdf Accessed Sep 2012