Using rosiglitazone (Avandia) in combination with standard diabetes treatments (metformin or a sulfonylurea) to lower blood glucose in type 2 diabetics does not increase the risk of cardiovascular disease or death. However, the study confirms that using rosiglitazone more than doubles the risks of heart failure, and also increases the risk of fractures, mainly in women. The findings of the RECORD study are published in an Article Online First and in an upcoming edition of the Lancet. They are being simultaneously presented at the American Diabetes Association (ADA) meeting in New Orleans, USA.
Rosiglitazone belongs to a class of drugs called thiazolidinediones, and has been proven by numerous studies as an effective agent to control blood glucose. But studies have also suggested an increased risk of heart attacks caused by the rosiglitazone, and concern about adverse effects has reduced its use. In this randomised trial, Professor Philip Home, The Medical School, Newcastle University, UK, and colleagues looked at 4447 patients with type 2 diabetes already on either metformin or a sulfonylurea with a mean haemoglobin A1c concentration* (HbA1c) of 7.9%. Patients were assigned received addition of either rosiglitazone (2220 patients) or to a combination of metformin and sulfonylurea (control group) (2227). The primary endpoint was cardiovascular hospitalisation or cardiovascular death.
The researchers found that 321 people in the rosiglitazone reached the primary endpoint compared with 323 in the control group – ie, no statistically significant difference. They also found that heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the control group—thus risk of heart failure was more than doubled for rosiglitazone patients. The risk of arm and lower leg fractures also increased by 57% in patients given rosiglitazone—although the increased risk for women (82%) was much higher than that for men (23%).
The authors say*: "It is good to have robust evidence that this useful medication does perform similarly to other glucose-lowering medications in regard of cardiovascular events. It is also good to see it perform better in controlling blood glucose in the longer term. The data on fractures and heart failure are known class effects, and here the study provides useful data to help clinicians and people with diabetes decide when it is not safe to use rosiglitazone."
They conclude: "What are the clinical implications for the future use of rosiglitazone? Rosiglitazone is not recommended for people with a history of heart failure or with previous problems that might have led to myocardial dysfunction. Rosiglitazone should be used with caution in women at high risk of fractures. Although our evidence is insufficient to rule out a small increased risk of myocardial infarction caused by rosiglitazone when compared with other glucose-lowering agents, rosiglitazone does not increase overall cardiovascular morbidity or mortality."
In an accompanying Comment, Dr Ravi Retnakaran and Dr Bernard Zinman, Mount Sinai Hospital, Toronto, and University of Toronto, Canada, say that half-maximum doses of rosiglitazone (or a related drug pioglitazone) in combination therapy could be considered as it is generally accepted that half-doses give better-than-half results, while limiting side-effects. They conclude: "This combination therapy is currently being assessed for the prevention of diabetes in individuals with impaired glucose tolerance. If the efficacy of this strategy is confirmed, we might be able to find the optimal way to use this class of medications in the treatment of type 2 diabetes."
Professor Philip Home, The Medical School, Newcastle University, UK T) +44 (0)7785 251736 E) philip.home@newcastle.ac.uk
For Dr Bernard Zinman, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, and University of Toronto, Canada please contact Nikki Luscombe, communications, T) +1 416 586-4800 ext. 2046 E) zinman@lunenfeld.ca / luscombe@lunenfeld.ca
For full Article and Comment, see: http://press.thelancet.com/recordada.pdf
Note to editors: *Quote direct from Professor Home and cannot be found in text of Article
**HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range (that found in healthy persons who do not have diabetes), is about 4%—5.9%. Patients with diabetes usually have HbA1c levels above 6.5%.
Part 2 of the American Diabetes Association meeting press release, containing 3 further articles, will be issued early US time tomorrow(Fri 5 June), with an embargo of 1730H New York time (1630H New Orleans) Monday 8 June.
Journal
The Lancet