Time in Range, Quality of Life Gain Attention at FDA Diabetes Workshop

An FDA workshop this week brought together patients, advocates, researchers, and leaders from the pharmaceutical industry to ask the question: other than glycated hemoglobin (A1C), what measures should regulators use to decide if new therapies are good for people with diabetes?

The workshop, titled "Diabetes Outcome Measures Beyond Hemoglobin A1C,” even brought out FDA Commissioner Robert M. Califf, MD, a cardiologist; and Robert Temple, MD, FDA deputy director for Clinical Science at Center for Drug Evaluation and Research. Also on hand were officials from Canadian and European regulatory agencies, according Kelly Close, founder of diaTribe.org and president of Close Concerns.

“The meeting was very positive and very collaborative,” said Close, who spoke with The American Journal of Managed Care after attending the workshop. “We felt like the FDA really wanted to listen.”

The session comes amid growing concern that too much fixation on A1C, which represents a person’s 3-month average plasma glucose concentration, overlooks other indicators of health and well-being that are important to people living with the disease. Advocates and researchers alike are increasingly interested in treatments that limit day-to-day or hour-to-hour fluctuations in blood glucose, prevent episodes of hypoglycemia, and allow people with diabetes to fully participate in activities without self care consuming so much time.

According to Close, 2 key issues emerged for future discussions at FDA: 1) the need to evaluate whether a therapy can maximize “time in range,” or the amount of time during the day that a person is neither above nor below recommended blood glucose levels; and 2) the need to measure a therapy’s ability to improve quality of life. According to Close, the European Medicines Agency representative discussed use of a treatment-related impact measure (TRIM).

Ahead of the workshop, diaTribe conducted an online survey among persons with diabetes and presented results at the session. The 3455 responses included 1025 from persons with type 1 disease (T1D), 1150 from persons with type 2 disease (T2D) using insulin, and 1280 from persons with T2D not using insulin.

The survey measured 16 qualify of life components and found:

• 32% of respondents with T2D not using insulin reported “not having energy for new challenges or opportunities”
• 46% of respondents with T2D using insulin reported “not being physically able to do what you want”
• 52% of respondents with T1D reported “worrying too much about money”
• Only 38% of respondents with T2D using insulin reported “not feeling stressed or anxious”
• 48% of respondents with T1D reported “not getting enough sleep”

Less than one-third of all 3 groups reported being feeling “very successful” with their current therapies in “emotional well-being,” and less than one-third in both the T1D group and T2D group using insulin reported being “very successful” in managing the burden of diabetes care.

The presentation included testimonials from patients who described being governed by a disease around the clock—for T1D persons especially, it controlled every bite of food, every moment of exercise, every change of schedule. But a different problem—denial—confronted those newly diagnosed with T2D.

One mother who had lived with T2D for 33 years, and had seen her own mother die of complications, described efforts to work with an adult son diagnosed at age 46. “I don’t think he understands the seriousness of the disease. He has seen me check and not eat the fun stuff, but I don’t think he gets it. Cuts me off every time I want to talk to him.”

Close noted that all 3 groups of patients ranked the challenge of staying in range as their top concern. “Time in range really defined the daily experience of living with diabetes,” she said. All day long, people with diabetes are making adjustments, whether it’s food, drink, insulin, other therapy, exercise, or rest. And that shows up in research that reports higher rates of depression among persons with diabetes.

At the 2014 Scientific Sessions of the American Diabetes Association (ADA), William Polonsky, PhD, CDE, described it this way: “The day someone is diagnosed, they’ve just been given a new job for the rest of their life,” one that doesn’t pay and has “no days off.”

“This is a 24/7 disease,” Close said. “Patients don’t get a break from the stress.” While adherence was not a particular focus of the workshop, she said there’s an obvious connection between the stress of managing diabetes and adherence.

There are signs the research community wants to tackle the “roller coaster” that Close and others describe. At the ADA sessions in June 2016, a session on clinical trials involving SGLT2 inhibitors to treat T1D discussed this precise problem. Maria Alba, MD, said despite the introduction of better insulins, patients still experience a “glycemic roller coaster” throughout the day.

“There is a huge medical need in this patient population to find different medical treatments to avoid these highs and lows,” she said.

A few days before the workshop, a new paper by Mayo Clinic researchers found that years of focus on getting A1C below 7% has produced little evidence of microvascular or macrosvascular benefit. The A1C monopoly has meant that drug developers are not pursuing therapies that would prevent complications or other problems in diabetes, they found.