Leaping Into the Unknown: PHROG Trial Explores Hypoglycemia Defense in T1D

For people with Type 1 diabetes (T1D), low blood sugar episodes—also known as hypoglycemia—can strike fast and hard. The body’s natural defense is to release hormones like glucagon to raise blood sugar levels. But in many patients with T1D, this safety system is impaired. A recent clinical trial set out to test whether a new drug could help restore that line of defense.

Researchers at AdventHealth’s Translational Research Institute (TRI), including Anika Bilal, Dr. Anna Casu, and Dr. Richard Pratley, were part of the national team behind the newly published study exploring a GPR119 agonist called MBX-2982.

This phase 2a clinical trial involved 18 adults with T1D who were carefully monitored under controlled conditions using a “hyperinsulinemic-hypoglycemic clamp”—a gold-standard method to evaluate how the body responds to dropping glucose levels. Participants took MBX-2982 or a placebo over two weeks, with the goal of testing whether the drug could stimulate the body’s hormone-based counterattack to hypoglycemia.

The Verdict? It’s a Mixed Bag.

MBX-2982 didn’t significantly boost glucagon, epinephrine, or other key hormonal responses during low blood sugar events. That means it didn’t deliver the hoped-for effect of strengthening the body’s protective response during hypoglycemia.

However, there was one encouraging sign: when participants ate a meal, their GLP-1 hormone levels rose by 17% after taking MBX-2982 compared to placebo. GLP-1 plays a role in digestion and blood sugar regulation, and the increase indicates the drug successfully activated the GPR119 receptor as designed.

“While it didn’t enhance the glucagon response, the fact that we saw increased GLP-1 suggests the drug engaged its target,” said Anika Bilal, one of the study’s lead investigators from TRI. “That’s important information that helps guide future development of therapies for people with T1D.”

Though the trial didn’t lead to an immediate breakthrough, it contributes valuable insights to the search for safer, smarter treatments for Type 1 diabetes—especially during life-threatening hypoglycemic events.

“Every step like this helps us learn what works, what doesn’t, and where to go next,” said Dr. Pratley. “It’s how we move closer to better outcomes.”

The study was published in Diabetes.