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Composite endpoints beyond HbA1c may better predict diabetes outcomes
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SAN DIEGO — An HbA1c measurement does not tell the full story about glycemic variability in patients with type 1 and type 2 diabetes and is not the best metric to assess the efficacy of diabetes interventions, according to a speaker here.
Since the landmark Diabetes Control and Complications Trial in the early 1990s, change in HbA1c has been the traditional metric for determining the efficacy of any diabetes intervention, said Robert A. Vigersky, MD, medical director of Medtronic Diabetes. However, the measurement leaves many questions unanswered.
Robert A. Vigersky
“HbA1c is, I think, woefully inaccurate,” said Vigersky, speaking at the American Association of Diabetes Educators annual meeting. “It doesn’t tell you what the time in range is. It doesn’t tell you about frequency, duration or severity of hypoglycemia. It doesn’t tell you about the frequency, duration or severity of hyperglycemia. It doesn’t tell you about glycemic variability. And because of that, we’re in a dilemma.”
Several new classes of medications and technologies have emerged that have been shown to decrease HbA1c with no effect on hypoglycemia, Vigersky said, whereas others have an effect on hypoglycemia with no effect on HbA1c.
“So, how do we think about these [interventions]?” Vigersky said. “How do we compare them to one another in an effective way? That’s where composite metrics come in.”
Any reliable composite metric should provide a “glucose-centric” and more comprehensive understanding of an intervention’s effect, Vigersky said. That means any metric would include HbA1c and hypoglycemia measurements, but, ideally, would also incorporate other patient-centric outcomes, including weight or even cost or quality-of-life measures, Vigersky said.
In a review of the literature, some researchers have already attempted to apply composite metrics in several ways, Vigersky said. Some have presented existing data in new visual representations; others have used numeric presentations, and others have combined visual and numeric representations.
The results, Vigersky said, better depict data in previous studies to predict diabetes outcomes.
Vigersky cited several examples of large trials, including the CANTATA and ASPIRE trials, where a composite metric was retrospectively applied to better predict which therapies increased or decreased hypoglycemia, weight or HbA1c. The metric could also be applied to psychoeducational interventions, he said.
New composite metrics are not going developed quickly, Vigersky stressed. Moving forward, Vigersky said, pharmaceutical companies should incorporate continuous glucose monitoring into all studies, providing researchers with the data to apply to any new composite metric. In addition, a uniform definition for hypoglycemia must be established, he said.
“We have to present evidence to [regulators] to show that [a new metric] is meaningful,” Vigersky said. “I think that we can do that by applying these concepts retrospectively. The professional societies have to organize together, and organize a consensus conference to get a consensus on a measure of hypoglycemia. That’s a start. Then we can get to the best composite metric. Some way of expressing the data in a meaningful way, or with a single number — a q-score, if you will — that will have some clinical meaning.”
The idea, Vigersky said, is to think of glucose as a vital sign, not HbA1c.
“We need to do better on behalf of our patients,” Vigersky said. “I think, in the future, we’re going to have a multicomponent single value. It took 20 or more years for everyone to buy into HbA1c and understand what it represented. The great thing was the DCCT trial used HbA1c. Changing the conversation isn’t going to happen overnight, but unless we start to address it, it isn’t going to happen.” – by Regina Schaffer
Reference: Vigersky R. F26. Looking beyond A1c as the Gold Standard Diabetes Outcome. Presented at: AADE 2016; Aug. 12-15, 2016; San Diego.
Disclosure: Vigersky is medical director for Medtronic Diabetes.