Too Much Focus on Tight A1C Control May Be Misguided in Diabetes Care, Mayo Clinic Study Finds

Focusing on lowering glycated hemoglobin (A1C) to the exclusion of other measures may not be in the patient’s best interest in diabetes care—and may prevent researchers from working on more novel therapies, according to a new paper by researchers at the Mayo Clinic.

Victor Montori, MD, and Rene Rodriguez-Gutierrez, MD, of the Knowledge and Evaluation Research Unit, published their findings in Circulation: Cardiovascular Quality and Outcomes. They reviewed a decade’s worth of journal articles and clinical practice guidelines (2006-2015), seeking statements that discussed the relationship between tight glycemic control and preventing diabetes complications.

They compared their findings with 20 years' worth of evidence on how maintaining tight glycemic control affects microvascular and macrovascular outcomes. They found that keeping A1C lower than 7% had no statistically significant impact on microvascular outcomes that are important to patient quality of life, including end-stage renal disease that leads to dialysis, renal death, blindness, and clinical neuropathy. This was the case even though 80% of the practice guidelines and statements said that tight glycemic control would prevent those complications.

Maintaining control seemed to have some benefits for macrovascular complications. Keeping A1C at 7% or lower reduced the risk of nonfatal heart attack by 15%, but it had no effect on all-cause mortality or cardiovascular (CV) mortality. Stroke risk did not appear to decrease, and amputation risk was unclear. Published statements linking glycemic control to these complications shifted over time, from largely supportive (85%) to skeptical (20% to 30%) after publication of the landmark study, Action to Control Cardiovascular Risk in Diabetes (ACCORD).

The potential for diabetes therapies to cause CV risk has dramatically affected the drug development and approval process in the United States. Following the publication of a study that suggested rosiglitazone might be linked to increased risk of heart attacks, the FDA issued a 2008 guidance that requires the sponsors of all new diabetes and obesity therapies to conduct large-scale CV outcomes trials to confirm drug safety.

Measures of A1C, along with blood pressure and low-density lipoprotein cholesterol are among the basic metrics used to gauge whether health systems are delivering quality care. This has raised concerns that some patients may be given levels of medication they can neither tolerate nor afford to achieve small improvements in A1C.

Montori and Rodriguez-Gutierrez are among those sounding the alarm about this problem, and they are promoters of a concept called “minimally disruptive medicine.” They addressed this topic in a commentary (with Ian Hargraves, PhD) in the spring issue of Evidence-Based Diabetes Management.

In their current paper, Montori and Rodriguez-Gutierrez call for the consensus on tight glycemic control to be reconsidered in favor of more individualized treatment. Therapeutic research needs to be broader in scope, with more focus on complications. “Consider the list of evidence-based therapies recommended … to prevent retinopathy or neuropathy beyond glycemic control: none,” they write.

Patients in some countries outside the United States who have type 2 diabetes seem to live longer with fewer complications, they note, which suggests there are other solutions to long-term care.