How Can Hypoglycemia Be Addressed in Type 1 Diabetes?

By Lynn Kennedy, Helen Gao, and Kelly Close

A workshop hosted by the JDRF and Helmsley Charitable Trust brought together leaders in the field to discuss opportunities and advances in the treatment and possible prevention of hypoglycemia 

How do you address hypoglycemia in type 1 diabetes? This question was the central focus of a workshop hosted by the JDRF and Helmsley Charitable Trust last month. Leading thinkers from medicine, research, industry, and advocacy came together to discuss the current capabilities for preventing low blood sugar, as well as what could become possible in coming years.

At its core, the workshop was largely focused on a review of the basic science related to reducing and preventing hypoglycemia – from identifying as yet unanswered questions, to highlighting opportunities for innovation and challenges needing to be overcome. Presentation after presentation reinforced that hypoglycemia is a serious concern for many people with diabetes, and current therapies are not enough. The main takeaway for the future? Real progress is being made toward developing medications for hypoglycemia, but a key challenge to be overcome is figuring out how to measure and monitor hypoglycemia in clinical trials.

In many cases, the workshop raised more questions than answers. So much still isn’t known about hypoglycemia, particularly the causes and the effects of recurring hypoglycemia or decreased hypoglycemia awareness. Other big questions raised about the developing treatments for hypoglycemia included:

• What is the difference between a blood sugar of 55 mg/dl and 70 mg/dl?

• How does repeated hypoglycemia affect long-term health?

• Is there a way scientists can predict which people have higher risk for hypoglycemia?

• Is there a way that hypoglycemia awareness can be restored in people no longer able to feel that their blood sugar is low?

• Can clinical trials be designed differently so that better conclusions about hypoglycemia can be drawn?

• Can the body’s natural response to low blood sugars (i.e., releasing glucagon to naturally increase blood sugar) be restored to counteract hypoglycemia?

• And on and on!

These are some of the key questions that must be answered in order for better treatment approaches to be developed, especially those that are drugs and not devices. There are many people hard at work at addressing these questions; however, many presenters at the workshop said that more research funding is needed to support this important work.

And the absence of a solution for hypoglycemia has very real effects for those with diabetes. The 3,500 people living with diabetes who participated in a survey supported by The diaTribe Foundation last summer really emphasized this point. Feelings of success with current therapies were low across the board, while time spent in the range of 70 mg/dl to 180 mg/dl (in other words, time not spent in hypoglycemia or hyperglycemia) had a positive impact on feelings of mental well-being, as well as on the loved ones of people with diabetes (see here for more results from the survey).

Several of the renowned experts in attendance, including Drs. Anne Peters and Stephanie Amiel, further acknowledged that while technologies like continuous glucose monitoring (CGM) have made important strides in helping people prevent hypoglycemia, these devices are not without their limitations. For example, they aren’t always able to identify and provide notification of low blood sugars; therefore, solutions that address the underlying causes of hypoglycemia or that help restore hypoglycemia awareness may be needed.

Speakers also looked to the future of hypoglycemia, noting that the focus of current research is on developing a drug-based therapy for hypoglycemia – e.g., a daily pill or injection that could prevent hypoglycemia, possibly by restoring hypoglycemia awareness or restoring the body’s ability to respond to low blood sugars on its own.

One possibility along these lines to receive mention was Zucara Therapeutics, a Canadian biotech company developing a drug (an SSTR2 inhibitor) designed to restore the body’s natural glucagon response when blood sugar drops too low – essentially restoring the “safety net” that people without diabetes have. Although the drug hasn’t yet reached human trials, the company is looking for its therapy to become a nightly injection that helps to reduce low blood sugar overnight.

This approach has been likened to one commonly used in asthma treatment, where people take a variety of daily long-term asthma control medications in order to prevent asthma, complementing their use of “rescue” inhalers during acute asthma attacks. By this analogy, glucagon rescue pens are like the “rescue” inhalers, while the proposed regular hypoglycemia therapy (i.e., a nightly injection) would be similar to the longer-term asthma control medications. This would certainly require a shift in how people with diabetes and their healthcare providers think about hypoglycemia, but could be an interesting and welcome approach in the field. Additionally, while some people with severe fear of hypoglycemia may find relief in a medication like this (if it makes it all the way through trials and regulatory approval), it remains to be seen whether its benefit will be seen as greater than the burden of an extra injection a day.

While there is still some way to go to reduce the burden of hypoglycemia, current technologies like CGM are making important strides by “upping” the amount of glucose data available to help people with diabetes manage blood sugar. And automated insulin delivery (artificial pancreas) systems have also shown dramatic benefits for reducing hypoglycemia – in some cases, over 70%.

Many thanks go to the JDRF and Helmsley Charitable Trust for all their work convening leaders and advancing such an important discussion to people with diabetes!