Amsterdam, The Netherlands, Sept. 19, 2007 -- New research, including two studies presented this week at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD), further support the cardiovascular safety of ACTOS (pioglitazone HCI) and its benefits regarding improved blood glucose and blood lipid levels for patients with type 2 diabetes. The unique outcomes, including some clinical practice results, reinforce the consistency of pioglitazone data and underscore that ACTOS has different effects from the other thiazolidinedione rosiglitazone due to differences in molecular structure.
New research [1] presented at EASD has shown that therapies which include pioglitazone are associated with significant reductions in the risk of stroke or myocardial infarction (MI) compared to non-thiazolidinedione therapies. This retrospective analysis of case records from a large managed care database of diabetes patients have shown that the adjusted relative risk of stroke for the pioglitazone group was 20 percent lower than the group not receiving pioglitazone. Likewise, the risk of heart attack over the study period was 38 percent lower in patients receiving pioglitazone than in those taking an anti-diabetes drug regimen that did not include pioglitazone. John Betteridge, Professor of Endocrinology and Metabolism at University College, London said: “The results of this analysis are very welcome and support the findings from the PROactive study of pioglitazone for secondary prevention of vascular events which showed a reduction in stroke and heart attack in this high risk population.”
In addition, the GLAI study [2] , also presented at EASD, further reflects the cardioprotective strength of pioglitazone. A new analysis of data from the first three months of this six-month head-to-head study of pioglitazone and rosiglitazone, in which the endpoint was the change in serum lipids, demonstrated that initial treatment with a starting dose of pioglitazone (30 mg) was more effective than a starting dose of rosiglitazone (4 mg) in improving blood glucose (HbA1c) levels and lipid levels. Also, researchers found that in addition to lowering HbA1c significantly more than rosiglitazone, pioglitazone also significantly decreased triglyceride levels and non-HDL cholesterol (a predictor of cardiovascular death), and markedly improved HDL-C levels (“good” cholesterol) versus rosiglitazone. “A likely explanation for the different effects on heart attack and strokes between the two drugs could be the favourable effect of pioglitazone in increasing HDL cholesterol without adverse effects on LDL as demonstrated in the GLAI study,” said Professor Betteridge.
The data presented at EASD add weight to a growing body of evidence including newly published findings from a large retrospective cohort trial published recently in the journal of Pharmacoepidemiology and Drug Safety [3] , which showed that pioglitazone is associated with a 22 percent relative risk reduction of hospitalization for acute myocardial infarction in patients with type 2 diabetes compared to rosiglitazone. In addition, they correlate with findings from a meta analysis published in the Journal of the American Medical Association [4] which demonstrated that pioglitazone reduces the risk of heart attack, stroke or death by 18 percent in patients with type 2 diabetes.
Notes to editors
About pioglitazone
Pioglitazone was approved by the European Medicines Agency for the treatment of type-2 diabetes in October 2000. The original label was most recently extended in January 2007. In Europe, pioglitazone is indicated in the treatment of type 2 diabetes mellitus as:
monotherapy
- in patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance
dual oral therapy in combination with
- metformin, in patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin
- a sulphonylurea, only in patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite maximal tolerated dose of monotherapy with a sulphonylurea.
triple oral therapy in combination with
- metformin and a sulphonylurea, in patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy.
Pioglitazone is also indicated for combination with insulin in type 2 diabetes mellitus patients with insufficient glycaemic control on insulin for whom metformin is inappropriate because of contraindications or intolerance
Takeda also manufactures COMPETACT which combines two widely used diabetes treatments (metformin and pioglitazone) in a convenient single tablet, to be taken twice daily. COMPETACT was first launched in Europe in October 2006.
COMPETACT 15mg/850mg tablets contains 15mg pioglitazone as hydrochloride and 850mg of metformin hydrochloride. Indication: Treatment of type 2 diabetes mellitus patients, particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.
About PROactive
PROactive (add reference) was a prospective, randomized, placebo-controlled outcomes trial. The PROactive study included 5,238 patients with type 2 diabetes and a history of macrovascular disease, who were force titrated up to 45 mg daily of either ACTOS or placebo. [5] In this study, there was no difference in the number of macrovascular events between standard of care and ACTOS, and standard of care alone. Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone.
The ACTOS Summary of Product Characteristics was recently revised by the EMEA to include this reassuring cardiovascular safety data. ACTOS is the only thiazolidinedione (TZD) with safety data from a cardiovascular outcomes trial in its label.
About Takeda in Europe
Takeda Pharmaceuticals Europe Ltd, based in London, UK, supervises the overall business activities of Takeda’s subsidiaries in Europe through promoting pan-European strategies.
Takeda Global Research & Development Center, Inc., based in Deerfield, Ill., USA, and London, U.K., is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and is responsible for Takeda’s clinical research and development in the U.S. and Europe.
Takeda Pharmaceutical Company Limited, located in Osaka, Japan, is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. Additional information about Takeda is available through its corporate website, www.takeda.com
ACTOS (pioglitazone HCl) is a registered trademark of Takeda Pharmaceutical Company Limited.
[1] Y. Xu et al Risk of Stroke and Myocardial Infarction Are Reduced in Patients with Type 2 Diabetes Treated with Pioglitazone: Results of a Retrospective, Claims-Based Study. PS130 / Abstract #1257. Presented at EASD on 18 September, 2007.
[2] T McCall et al. Effects of 30 mg of Pioglitazone vs 4 mg of Rosiglitazone on Hyperglycemia and Dyslipidemia: Results from a Head-to-Head Trial. PS80 / Abstract #0865. Presented at EASD on 19 September, 2007.
[3] Gerrits et al. A comparison of pioglitazone and rosiglitazone for hospitalization for acute myocardial infarction in type 2 diabetes. Pharmacoepidemiology and drug safety. 2007. Available online at www.interscience.wiley.com. [Last accessed 6 September 2007].
[4] Lincoff et al. Pioglitazone and the risk of cardiovascular events in patients with type 2 diabetes mellitus. JAMA. 2007; 298 (10):1216-1218
[5] JA Dormandy et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone clinical trial in macroVascular events) a randomised controlled trial. Lancet. 2005. 366:1279-89.