Individualized goals, risk management key in reducing hypoglycemia in older adults

Older adults with diabetes are at the greatest risk for adverse events, including hypoglycemia, from diabetes medications, yet many gaps remain when it comes to identifying and preventing hypoglycemic episodes in this population, according to several experts who spoke during a daylong FDA forum Tuesday.

“The hypoglycemia we see in our emergency departments and hospitals is only the tip of the iceberg,” Andrew J. Karter, PhD, a research scientist with Kaiser Permanente Northern California, said during a presentation on hypoglycemia medication safety efforts at the FDA Center for Drug Evaluation and Research. “At Kaiser, we have over 300,000 patients with diabetes ... and we found that about half a percent annually experience hypoglycemia-related utilization. But when you ask the patients, 11% annually reported a severe hypoglycemic event. Based on that, we estimated that 95% of severe hypoglycemic event are not clinically recognized.”

Stakeholders from the diabetes community attended the FDA’s public workshop, hosted by professional affairs and stakeholder engagement staff, on reducing the risk of preventable adverse drug events associated with hypoglycemia in the older population. Speakers touched on several key issues throughout the day, including the importance of glycemic control targets for older patients with diabetes, identifying medication safety efforts, risk prediction tools and future areas of research.

“Patients do not necessarily understand their hypoglycemia symptoms and have trouble reporting them,” said Nadine Shehab, PharmD, a senior service fellow with the division of health care quality promotion at the CDC. “There is much work that needs to be done ... to capture the full scope of these adverse events.”

Hypoglycemic adverse events are the third most common adverse drug event in nationally represented samples of Medicare beneficiaries, Shehab said. Of the 1.3 million hospital visits for adverse drug events in 2013-2014, 14% involved diabetes medications, she said, and insulin is the second most implicated drug based on national surveillance data.

“Those [aged] 80 years or older have been identified by surveillance data as having the highest risk for ED visits,” Shehab said. “We know that patients experience hypoglycemic episodes that are never reported or go unrecognized ... and these data highlight a need to report hypoglycemic episodes.”

‘Tailored to the patient’

Older adults often have comorbid conditions that put them at greater risk for hypoglycemia, including hypertension, hyperlipidemia and atherosclerotic disease, said Gerardo Moreno, MD, executive director of UCLA PRIME and associate professor in family medicine at the David Geffen School of Medicine at UCLA. Additionally, quality of care is often suboptimal for older adults, and there is little randomized controlled trial evidence to support specific care recommendations for the older population with diabetes.

The risk for hypoglycemia further increases for older adults with cognitive impairment, Moreno said.

“But we cannot always extrapolate to older adults with diabetes,” Moreno said. “Older adults are a very heterogeneous population. We all have relatives who are high functioning, who swim, etc, but then we have frail elders with limited mobility. Some may be on one medication, and some are on 12 medications. For an 80-year-old who may have terminal cancer, does it make sense to drive down the HbA1c?

“If we have a frail adult who is 80 years old ... we may want to focus on blood pressure or lipids, and not glycemic control,” Moreno said. “That all has to be tailored to the patient.”

Karter said there is a misconception that hypoglycemia is not a concern for patients with type 2 diabetes, which adds to the current problem.

“I call it a clinician form of hypoglycemia unawareness,” Karter said. “Traditionally, the messaging around care for patients with diabetes is focused around achieving good glycemic control — the ‘lower is better’ myth. There is little attention paid to hypoglycemia prevention.

“Targeting high-risk patients becomes particularly compelling when there is an effective intervention,” Karter said.

Risk prediction tools

Nationwide, health systems can manage hypoglycemia risk by implementing inexpensive risk prediction tools and collecting self-reported outcomes, said Nilay D. Shah, PhD, a consultant in the division of health care and policy research at Mayo Clinic in Rochester, Minnesota.

As part of the national Transforming Clinical Practice Initiative, Mayo Clinic’s Practice Transformation Network is providing 90 primary care practices with technical assistance related to integrated behavioral health, readmissions, chronic disease management and medication therapy management — including collecting data on hypoglycemia.

In implementing the hypoglycemia risk prevention tool, Shah said, researchers observed that multiple factors influence hypoglycemia risk.

“One of these reasons patients get into trouble is they get their insulins mixed up, or the doses are wrong ... and then the food issue comes up as we think about implementing this,” Shah said. “We’ve realized that the likely intervention will be outside the patient-clinician encounter. It’s a heterogeneous problem, even just based on our initial experience so far.”

William Lee, DPh, MPA, FASCP, pharmacy system director for Carilion New River Valley Medical Center in Christiansburg, Virginia, recommended boosting efforts to collect patient-reported data on hypoglycemic episodes, as well as taking advantage of the patient-pharmacist relationship to promote risk mitigation strategies that reduce hypoglycemia.

“Patients only see their physicians once or twice a year, but they see the pharmacist 12 to 35 times a year,” Lee said during public comment. “[Pharmacists] actually know more about what is going on, and can actually tell [patients] what is going on to prevent these hypoglycemic reactions.

“As a pharmacist, as a clinician and a researcher, my frustration is I have to wait 2 years for someone to publish something and then say, ‘Should I adopt it?’” Lee said. “We have to stop waiting, and we have to start somewhere.”

‘Beyond Hb A1c’

Speaking during a public comment portion of the meeting, Medha Munshi, MD, associate professor at Harvard Medical School and director of the Joslin Geriatric Diabetes Program, said identifying and quantifying hypoglycemia in older adults remains a challenge because HbA1c is not predictive of hypoglycemia incidence in this population.

“HbA1c levels do not correlate with hypoglycemia in older adults,” Munshi said. “I don’t say this to be controversial ... but for the risk of hypoglycemia, it is not an adequate measure.”

For older patients, a deintensification of the insulin regimen can usually reduce the risk for hypoglycemia without worsening glycemic control, Munshi said.

“It’s a costly business to do larger studies on older individuals,” Munshi said. “We need to rely on good tools and effective algorithms to help providers, endocrinologists, geriatricians, nurse practitioners to back off [medications].”

For patients with type 1 and type 2 diabetes, expanding the hypoglycemia definition beyond what is considered “severe” reveals an even greater problem, said Robert E. Ratner, MD, FACP, FACE, former chief scientific and medical officer for the American Diabetes Association.

“When you begin to look at hypoglycemia beyond severe hypoglycemia, what you see is that almost 80% of type 1’s and over 50% of type 2’s experience hypoglycemia at least once a month, and many have it more than once a week,” Ratner said during a public comment portion of the meeting. “We’re missing an enormous amount of significant morbidity in association with hypoglycemia.”

The consequences of this unrecognized and untreated hypoglycemia, Ratner said, include increased length of hospital stay, increased morbidity and increased cost.

“But that’s not the whole story,” Ratner said. “Asymptomatic hypoglycemia carries morbidity and potential mortality with it as well. The reality is you don’t have to be symptomatic to have morbidity associated with diabetes. You have to think in terms of the spectrum of hypoglycemia.”

Ratner advocated for recognizing hypoglycemia “as an outcome, not a side effect,” for FDA reviews and performance measures, as well as moving beyond the “severe” designation to capture the full range of hypoglycemia experiences.

“In order to discover the rest of the iceberg, we need to incorporate CGM in most of our regulatory endeavors,” Ratner said. “It doesn’t need to be [used with] every patient in every study, but in sufficient numbers to identify unrecognized hypoglycemia.” – by Regina Schaffer