In a personal view article published online today in the journal The Lancet Diabetes & Endocrinology, researchers are calling for the systematic evaluation of heart failure to be included routinely in clinical outcome trials of glucose-lowering drugs.
Lead author Prof John McMurray of the University of Glasgow, together with DTU Director Prof Rury Holman and colleagues from Canada and the USA, are concerned that heart failure is rarely considered as a key outcome, or even part of composite cardiovascular outcomes, in large-scale clinical trials of glucose-lowering drugs. This is despite evidence that hospitalisation for heart failure is one of the most common and prognostically important complications of diabetes.
Until now, a drug's ability to reduce elevated glucose levels in people with diabetes was used in clinical trials as a 'surrogate' - a reflection of its ability to reduce the risk of microvascular disease, and possibly cardiovascular risk. But recent evidence is emerging that the opposite may be true - that some glucose-lowering drugs may actually be detrimental to cardiovascular health, including increasing the risk of heart failure. As a result, the FDA and EMA have introduced new regulations that require all new glucose-lowering drugs to be tested in cardiovascular outcomes trials.
So far, such cardiovascular outcomes trials have typically used major adverse cardiovascular events (MACE), that is cardiovascular death, heart attack and stroke, as their primary outcome. Heart failure, however, is not included here, despite it being more common than any of these other cardiovascular outcomes, especially in patients with advanced diabetes, and more closely associated with premature death. Its omission as a key endpoint in clinical trials could mean that important beneficial or harmful cardiovascular effects of glucose-lowering drugs being tested are being overlooked.
"Hospital admission for heart failure is a not uncommon cardiovascular complication of diabetes that has a poor prognosis," says Prof Holman. "It is essential that we fully understand any impact that glucose-lowering drugs may have on the development of heart failure. Some ongoing cardiovascular outcome trials of glucose-lowering drugs are systematically evaluating heart failure but unfortunately, many are not."
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