Intensive Glucose Level Treatment in Diabetes Can Cause Complications

Treatment nearly doubled the risk of severe hypoglycemia that required medical attention in patients with type 2 diabetes.

Over-testing and intensive treatment of HbA1C levels in adults with type 2 diabetes can lead to serious harm and complications, such as hypoglycemia.

In a study published in JAMA Internal Medicine, authors wanted to see if intensive and overtreatment could increase risk complications in type 2 diabetes patients.

“At first, we were surprised to find how much over testing for HbA1C is occurring among adults of all ages with type 2 diabetes who were already well-controlled,” said lead study author Rozalina McCoy, MD. “But, then, we realized that not only were patients being tested frequently, they were also being treated with more medications than we would expect considering how low their HbA1C already was. So, this led us to do this study — to see how frequently patients are treated so intensively that they may be over treated and what that does to their risk of hypoglycemia.”

The results of the study showed that intensive treatment nearly doubled the risk of severe hypoglycemia that required medical attention, including hospitalization. This was found to be especially true in older patients and those with serious chronic conditions.

A majority of professional societies recommend targeting HbA1C levels less than 6.5 or 7% with individualized treatments based on a patient’s age, additional medical conditions, and which patients are at risk of therapy-induced hypoglycemia.

“Treating patients to very low HbA1c levels is not likely to improve their health, especially not in the short term, but can cause serious harms, such as hypoglycemia,” McCoy said.

During the study, researchers defined intensive treatment as being treated with more glucose-lowering medications than clinical guidelines considered necessary, based on a patient’s HbA1C level.

Patients taking any medications with HbA1C levels less than 5.6% were considered intensively treated. Those who had HbA1C levels between 5.7 and 6.4% (prediabetes range) and who were using 2 or more medications during the test or had started additional medications after the test were considered to be intensively treated. Lastly, those with HbA1C between 6.5 and 6.9% who had treatment intensification with 2 or more drugs or insulin were considered intensively treated.

Medical claims, as well as pharmacy and laboratory data, were examined during the study from 31,542 stable and controlled type 2 diabetes adult patients who were included in the OptumLabs Data Warehouse between 2001 and 2013.

None of the patients had any obvious indications for tight glycemic control, none had been treated with insulin, and none had severe episodes of hypoglycemia in the past.

“Our goal was to specifically assess the degree to which intensive treatment — not other known risk factors, such as prior hypoglycemic events or insulin therapy – caused hypoglycemia,” McCoy said. “We also wondered if young and healthy patients may be better able to tolerate intensive treatment than older patients or those with complex medical problems, so we specifically looked at the impact of intensive treatment on these 2 groups separately.”

Researchers separated patients based on whether they were clinically complex or not to help identify patients who are more likely to have treatment-related adverse events after adding glucose-lowering medications. American Geriatrics Society defines clinically complex as being 75-years-old or older, having dementia or end-stage kidney disease, or having 3 or more serious chronic conditions.

There were 18.7% of clinically complex patients and 26.5% of non-complex patients treated intensively.

The results of the study showed that clinically complex patients had nearly double the rate of severe hypoglycemia compared to non-complex patients. Furthermore, intensive treatment increased this by an additional 77% from 1.74 to 3.04% over 2 years.

“This means that 3 out of 100 older or clinically complex patients with diabetes who never had hypoglycemia before, whose HbA1C is within recommended targets, and who are not on insulin, will experience a severe hypoglycemic episode at some point over 2 years,” McCoy said. “This does not even capture the more mild episodes of low blood sugar that patients can treat at home, without having to go to the doctor, emergency department or hospital.”

The study’s findings reveal the potential detrimental effects that comes with overtreatment.

“These findings are concerning for many reasons,” McCoy said. “Overtreatment results in greater patient burden, higher risk of medication side effects, and more severe hypoglycemia, which can lead to serious injury and even death. It adds more unnecessary costs for patients and the health care system. And, at the same time, there is often little or no benefit from such intensive treatment — not in the long term and certainly not in the short term.”

Authors noted that physicians should be more mindful when choosing medications, weighing the good versus the bad and understanding that less can be more.

“As clinicians, we need to understand not only what tests and medications are necessary, but also determine which ones are not, and which ones may cause more harm than good,” McCoy said. “We need to individualize treatments to the needs and goals of our patients, and be comfortable saying 'sometimes, doing less is ultimately giving our patients more.' My hope is that others will be able to apply our findings in their practices for the benefit of patients everywhere.”