Should time in range replace HbA1c as the primary outcome metric for diabetes?
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Continuous glucose monitoring has completely revolutionized patient care.
If you’re talking about patient management, there is no question about the value of CGM and time in range, because HbA1c is really not worth anything for management.
HbA1c is not actionable. There’s nothing that HbA1c will tell you that will help the patient or the physician to change treatment in a specific way. CGM has completely changed that, because you are now able to analyze relationships and trends and focus on whether you should be maximizing time range, minimizing time below range or trying to reduce glycemic variability.
CGM is not just a way to record glycemic status, but is actually a guide for treatment. Studies have shown that just having a patient look at their CGM data will improve their glycemic control without discussing it with their prescriber.
For clinical trials and regulatory approval process, it is more complicated. The FDA has always used HbA1c and has not yet agreed to use time in range as the primary endpoint. The advantage of HbA1c is there is decades of experience where people have been able to tie HbA1c reduction to improved long-term diabetes complications.
The only point of discussion that remains now is when we will have enough data available on the correlation between time in range and those long-term diabetes complications. That research is happening already. Every clinical trial over the last 30 years has at least a subset of patients on CGM.
We really do not have a good idea what is the optimal metric from the CGM that will improve outcomes that everyone cares about. The fallacy of just looking at time in range is you also need to assess the other CGM metrics. Time in range is a first step. What everyone’s looking for is how do you correlate CGM metrics to long-term complications.
The FDA should do what it promised to do several years ago and make CGM metrics the primary endpoint. Only then can you decide within the framework of each trial, what is the regulatory hurdle for time in range, time below range, glycemic variability and patient-reported outcomes.
- For more information:
- George Grunberger, MD, FACP, MACE, is chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan.
We should use HbA1c and time in range to complement each other for people who have access to CGM.
HbA1c is a very well-established biomarker of glycemic control and an established surrogate for evaluating the effectiveness of glucose-lowering therapies. HbA1c is strongly linked to outcomes, and we have decades of data showing this.
The nice thing about time in range is it is a relatively simply metric. The nice thing about CGM technology is accuracy has improved over time and no longer requires finger-stick calibration, so now CGMs are widely used in high-income countries in type 1 diabetes. The American Diabetes Association and other organizations have made broader recommendations for the uses of CGM technology in anyone who is using multiple daily injections of insulin.
The usefulness of CGM in people with type 2 diabetes not on insulin, however, is not yet clear at all. I worry we are just extrapolating from small groups, mostly highly educated, not very diverse small populations with type 1 diabetes. That is one concern, because we have very little data on CGM in type 2 diabetes.
HbA1c is also a standardized measurement. It is monitored and reference labs work with manufacturers to standardize their methods. None of that exists yet for CGM. There is no reference material, they’re calibrated by the manufacturers, there is no attempt to harmonize them, there is no standardized oversight.
It can also be very hard for people with diabetes to get access to CGM and that’s just in the U.S. If we’re talking globally, there are many countries where you can’t even get an HbA1c, let alone a CGM.
Even if we removed all of the practical barriers to use of this technology, the major limitation is time in range is not linked to clinical outcomes in the same way HbA1c is. While data from type 1 diabetes is emerging, that is not the full population of people with diabetes.
We need data showing that time in range has value above and beyond HbA1c. Until we have data saying time in range is definitely better than HbA1c with respect to all of the key outcomes that we care about in diabetes, it’s a no-brainer that we have to figure out how to use these metrics in a complementary manner.
- For more information:
- Elizabeth Selvin, PhD, MPH, is a professor at the Johns Hopkins Bloomberg School of Public Health.
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