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Cardiovascular safety of antidiabetes drugs in doubt

Clinical trials need to assess heart failure risk

Jo Carlowe

Thursday, 13 March 2014

The heart risks of glucose-lowering drugs are being overlooked in clinical trials of antidiabetes drugs.

In a personal view*, published today in The Lancet Diabetes & Endocrinology journal, Professor John McMurray of The University of Glasgow and colleagues, reviewed evidence that shows that while some glucose-lowering drugs increase the risk of heart failure, this is rarely considered as a key outcome, or even part of composite cardiovascular outcomes, in clinical trials of glucose-lowering drugs.

Previously, the ability of an antidiabetes drug to lower glucose was used in clinical trials accepted as a surrogate of its ability to reduce the risk of microvascular disease, and possibly cardiovascular risk. Recent evidence has suggested, however, that some antidiabetes drugs may increase patients’ cardiovascular risk, despite their ability to effectively lower blood glucose. These findings have prompted the FDA and EMA to make new regulations requiring cardiovascular outcomes trials for new antidiabetes drugs.

Such cardiovascular outcomes trials have typically used so-called major adverse cardiovascular events (MACE) as a primary outcome. This combined outcome usually includes cardiovascular death, heart attack, and stroke. However, as McMurray and colleagues explain, heart failure can be more common than any of these other cardiovascular outcomes, especially in patients with advanced diabetes, and it is also more closely associated with premature death. Its omission as a key endpoint in clinical trials could mean that important cardiovascular effects of the glucose-lowering drugs being tested are being overlooked, say the researchers.

“Fortunately, some trials in progress are taking heart failure into account as a secondary outcome. But many others are neglecting to report this important complication as a key trial outcome. Until heart failure is systematically evaluated in clinical trials, the cardiovascular safety of antidiabetes drugs will remain uncertain,” concludes Professor McMurray.

*doi:10.1016/S2213-8587(14)70031-2

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