The role of A1c and CGM testing

For more than four decades, hemoglobin A1c has served as the cornerstone of long-term glycemic assessment, guiding diabetes diagnosis, risk stratification, and treatment decisions. Its durability stems not only from its technical strengths—standardization, reproducibility, and accessibility—but from the powerful clinical evidence that cemented its role. As a single biomarker obtained from a routine blood draw, A1c provides a comprehensive, validated picture of average glycemia and remains the only measure proven to predict long-term complications and the impact of therapy.

Yet diabetes care has evolved dramatically. With the explosion of GLP-1 therapies such as Ozempic, heightened public interest in tracking glucose, and growing patient access to continuous glucose monitoring technology, there is an urgent and highly relevant need for discussion to understand how we use diagnostic technology. In this article, William E. Winter, MD answers MLO’s questions on this topic.

HbA1c testing has been around for decades. What makes it so enduring as the “gold standard” in diabetes management? 

Following the discovery of insulin by Banting and Best in 1921, there was the hope that diabetes mellitus had been cured. Prior to the discovery of insulin, persons with type 1 diabetes rarely lived more than a year and certainly succumbed to the disease within 2 years of diagnosis.¹ While insulin was lifesaving for persons with type 1 diabetes, as the years and decades passed, physicians and their patients realized that diabetic complications were frequent and caused blindness, kidney failure, neuropathy and premature cardiovascular death. Thus, the paramount question for all physicians and persons with diabetes was as follows: “Is the development of diabetic complications dependent on the patient’s glycemic control, or are complications independent of glycemia?” If diabetic complications did indeed result from chronic hyperglycemia, the penultimate question became: “Does improved glycemic control decrease one’s risk of developing diabetic microvascular complications?”

Two studies published in the 1990s addressed these two questions. The Diabetes Control and Complications Trial (DCCT)² and the United Kingdom Prospective Diabetes Study (UKPDS)³ examined, respectively (and prospectively), persons with type 1 diabetes and persons with type 2 diabetes. Both studies came to similar conclusions: the severity of hyperglycemia, as measured by hemoglobin A1c, was correlated with the participants’ risk of developing microvascular complications (e.g., retinopathy, nephropathy, and neuropathy). Possibly even more important were their findings that improved glycemia, as measured by reductions in hemoglobin A1c, reduced the participants’ risks of developing microvascular complications. This spelled good news for the diabetes community: by maintaining plasma glucose as close as possible to the “normal range,” microvascular complications could be prevented. Thus, patients could improve their likely outcomes by reducing hemoglobin A1c levels.

These two studies demonstrate that hemoglobin A1c is an excellent marker of long-term risk for the development of complications. Since that time, researchers have discovered that modest elevations in hemoglobin A1c in persons without diabetes can predict the later development of type 2 diabetes and elevated hemoglobin A1c can be used to diagnose diabetes.

Therefore, hemoglobin A1c is the primary metric for the assessment of long-term glycemia that can predict diabetes, diagnose diabetes, and assess a person's risk for diabetic microvascular complications. No single biomarker (obtained by a single phlebotomy) provides the diversity of information that is provided by the measurement of hemoglobin A1c.

Hemoglobin A1c measurements are affordable, clinically available (being present on many highly automated platforms), highly standardized, accurate, and reproducible. There is less biological variability in hemoglobin A1c than measurements of plasma glucose. As well, hemoglobin A1c concentrations are stable throughout the day, and testing does not require fasting.

What evidence from landmark trials like the DCCT and UKPDS still resonates today in showing the importance of A1c? 

The DCCT⁴ and UKPDS⁵ findings are as valid in 2026 as they were in the 1990s. Higher levels of hemoglobin A1c predict an increased risk of diabetic microvascular complications. Possibly even more important is the fact that reducing hemoglobin A1c levels reduces one’s risk of developing such complications. These facts apply to all persons with diabetes regardless of whether or not a person with diabetes is insulin-treated.

What’s the value of HPLC technology for measuring A1c?

In various locations throughout the world, there is up to a 1%-4% risk of a patient having a hemoglobinopathy or thalassemia that could yield a clinically invalid hemoglobin A1c result when measured by a structural-based method (e.g., immunoassay, enzymatic, or boronate affinity). The laboratorian and clinician caring for the patient can be assured that hemoglobin A1c measurements reported using a charge-based separation method (e.g., HPLC or capillary electrophoresis) can detect the absence of hemoglobin A and can often suggest the presence of a hemoglobinopathy and/or thalassemia. Therefore, charge-based methods can reduce errors in reporting hemoglobin A1c, thereby improving patient care.

What has continuous glucose monitoring brought to diabetes care that wasn’t possible before?

Hemoglobin A1c and CGM are complementary and are “partners” in the care of patients with diabetes. Only hemoglobin A1c is validated as a measure of risk for the development of long-term diabetic complications, and only reductions in hemoglobin A1c have been shown to reduce the patient’s risk of developing such complications. However, hemoglobin A1c measurements do not inform the patient or their health care team as to how glycemic control can be improved (e.g., “normalized”). This is the role of self-monitoring of blood glucose (SMBG) and especially CGM. Prior to CGM, persons with diabetes might perform SMBG, at most, seven times per day, as a basis for adjusting medication dosages, diet, and exercise. With CGM, interstitial glucose can be measured every 5 minutes to develop a detailed glycemic profile. With these data in hand, the patient and their health care team can plan and implement a flexible regiment to improve glycemia measured as a reduction in hemoglobin A1c.

It should be noted that, in the U.S. at least, insurance companies will only cover the partial or full costs of CGM in persons with type 1 diabetes and persons with insulin-treated type 2 diabetes. Therefore, CGM is only available to a limited number of people with diabetes. Furthermore, the cost of CGM is not negligible. As well, wearing the CGM device, monitoring the CGM results, adjusting medications, and incorporating a healthy diet and exercise require a considerable commitment from the patient and their family. Not all CGM-eligible persons are able (or willing) to make and execute such a commitment. Lastly, while CGM is potentially a wonderful tool for improving glycemia, CGM is not used to predict or diagnose diabetes, which are functions provided by hemoglobin A1c measurements and not CGM.

How do patients respond differently when they see real-time data from CGM compared to periodic A1c results?

CGM and hemoglobin A1c assess different aspects of glycemia. CGM provides real-time data (and past data) whereas hemoglobin A1c is a summative measure of what has happened cumulatively in the last 2 to 3 months. By reducing their hemoglobin A1c concentration, patients can reduce their risk of developing diabetic complications. While it is assumed that improved glycemic control, as measured by CGM, will reduce the patient’s risk of developing diabetic complications, there are no prospective CGM studies analogous to the DCCT and UKPDS that prove this hypothesis.

A 2024 article in Clinical Diabetes reported the following key points regarding patients who use CGM (this is a direct quote from the article):⁶

• Ninety percent of survey respondents agreed that the majority of continuous glucose monitoring (CGM) sensors were accurate. However, only 79 and 78%, respectively, were satisfied with sensor performance on the first and last day of wear.
• Forty-two percent agreed that accuracy varies from sensor to sensor, with 54% experiencing skin reactions or irritation using sensors.
• Thirty-five percent were concerned about the impact of over-the-counter or prescription medications (e.g., cold and flu remedies or pain relief products) on sensor accuracy.
• Thirty-six percent agreed that inaccurate CGM alarms or alerts negatively affected daily life, and 34% agreed that they negatively affected diabetes management.

Many people believe that continuous glucose monitoring (CGM) will eventually replace A1c. Do you agree with that view? Why or why not?

I do not believe that CGM should replace hemoglobin A1c measurements. As described in my previous response, CGM and hemoglobin A1c are complementary, and they provide different information. CGM provides real-time glycemic data that can be used to determine day-to-day, minute-to-minute care. Hemoglobin A1c is retrospective providing information about average glycemia over the preceding 2 to 3 months. CGM is expensive, demanding, labor-intensive and is not available to all people with diabetes. If 10% of people in the U.S. have type 1 diabetes and 90% have type 2 diabetes, with 25% of these persons using insulin (and are thus eligible for CGM), assuming that all of these insulin-treated persons indeed used CGM, approximately 2 out of 3 people with diabetes would not have access to CGM (nor should it be assumed that they would benefit from CGM). Presently 40% to 50% of people with type 1 diabetes use CGM.⁷

With new therapies such as GLP-1 receptor agonists (e.g., Ozempic), how does the role of A1c testing or CGM change?

Novel therapies should not change the use of CGM or hemoglobin A1c measurements.

In an era of digital health and remote monitoring, where do you see A1c fitting into the workflow of the future diabetes clinic?

Hemoglobin A1c will continue to be used as currently recommended by the American Diabetes Association.⁸ Persons with glycemic control at or near to target should have their hemoglobin A1c measured every 6 months whereas persons with glycemia above the target range should be tested every 3 months.

Whereas point-of-care testing (POCT) devices for measuring hemoglobin A1c may be convenient, they have the following limitations: POC testing by staff takes staff away from direct patient care. Because POCT devices generally measure hemoglobin A1c in one sample at a time, POCT is inefficient when compared to central laboratory testing where measurements are automated. POCT for hemoglobin A1c is not as accurate or precise as central laboratory testing. Unless there is a dedicated POC testing staff coordinator, staff are usually not trained to appreciate the importance of quality control and quality assurance. POCT is more expensive than central laboratory testing.

If you could leave physicians with one key message about A1c and CGM, what would it be?

CGM and hemoglobin A1c are complementary measurements that are both important for the care of insulin-treated persons.

REFERENCES

1. Polonsky KS. The past 200 years in diabetes. N Engl J Med. 2012;367(14):1332-40. doi:10.1056/NEJMra1110560.
2. Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-86. doi:10.1056/NEJM199309303291401.
3. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-53.
4. Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-86. doi:10.1056/NEJM199309303291401.
5. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-53.
6. Holt E, Nguyen H, Bispham J, et al. Perceptions of continuous glucose monitoring systems in the T1D exchange diabetes registry: Satisfaction, concerns, and areas for future improvement. Clin Diabetes. 2024;42(1):104-115. doi:10.2337/cd23-0005.
7. Mayberry LS, Guy C, Hendrickson CD, McCoy AB, Elasy T. Rates and correlates of uptake of continuous glucose monitors among adults with type 2 diabetes in primary care and endocrinology settings. J Gen Intern Med. 2023;38(11):2546-2552. doi:10.1007/s11606-023-08222-3.
8. American Diabetes Association Professional Practice Committee. 6. Glycemic goals and hypoglycemia: Standards of care in diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S128-S145. doi:10.2337/dc25-S006.