Glucagon is a key driver behind experimental obesity drugs' remarkable weight loss, Duke School of Medicine researcher Jonathan Campbell argued at the American Diabetes Association's 86th Scientific Sessions.

"The drugs may be working so well in part because of glucagon," said Campbell, an associate professor in Duke's Division of Endocrinology and a member of the Duke Molecular Physiology Institute who has studied the hormone for more than a decade.

On Sunday, June 7, Campbell presented new animal data suggesting that activating glucagon receptors helps prevent the metabolic slowdown that typically accompanies weight loss. In his studies, animals receiving retatrutide, Eli Lilly's experimental triple-agonist drug that simultaneously targets GLP-1, GIP, and glucagon receptors, maintained their energy expenditure despite substantial weight loss.

The clinical numbers back up the science. Lilly announced on Saturday, June 6, that its Phase 3 TRIUMPH-1 trial showed participants on the highest dose of retatrutide lost an average of 70.3 pounds (28.3% of body weight) over 80 weeks. In a pre-specified extension through 104 weeks, participants with a baseline BMI of 35 or higher lost an average of 85 pounds (30.3%), a level historically associated with bariatric surgery.

Campbell argued for a fundamental reframing of glucagon's biological role. Rather than simply raising blood sugar during fasting, he said the hormone plays a central role in processing nutrients, burning fat, and supporting insulin function after meals. Early studies from his lab also suggest glucagon receptor activation can reduce liver fat and improve markers of liver injury.

The findings build on Campbell's prior work. A September 2025 study published in Science Advances, conducted in his lab in Duke's Carmichael Building with lab manager Danielle Leander and colleagues, revealed that pancreatic alpha cells produce far more bioactive GLP-1 than previously believed, blurring the line between glucagon-producing and insulin-supporting cells.

Campbell acknowledged that cost and long-term use remain challenges. Current GLP-1 obesity therapies run $149 to more than $1,000 a month, and he described the question of what happens when patients reach their goal weight as "one of the biggest challenges." Lilly has said additional TRIUMPH trial results for patients with type 2 diabetes and cardiovascular disease are expected later in 2026.