GLP1 and GLP2 medications have transformed diabetes and weight loss treatment, but they are still not “wonder drugs,” said Daniel Drucker, MD, during the Robert J. Lefkowitz, MD, Distinguished Lecture on Thursday, February 5, hosted by the Duke University School of Medicine.
Drucker, professor in the Temerty Faculty of Medicine and senior scientist at the Lunenfeld Tanenbaum Research Institute at Mt. Sinai Hospital, University of Toronto, is internationally recognized for discovering the biological actions of these hormones.
Named one of Time magazine’s Most Influential People of 2024, he emphasized that the medications “offer something for almost everyone,” with evidence showing benefits across multiple organ systems, including reduced blood pressure, lower inflammation, and kidney protection.
Some of these improvements are tied to weight loss, he said, while others occur independently of it. Yet major scientific questions remain about the mechanisms behind these drugs, with some studies in animal models producing conflicting results.
“We’re good at showing how GLP1s don’t work, but we haven’t figured out how they do work,” he said, adding that researchers are still determining which receptors are involved and where they are located.
Meanwhile, human clinical trials continue to show strong safety and benefit profiles. Drucker highlighted the SELECT trial, which demonstrated a 25% reduction in heart attacks and a 19% reduction in all-cause mortality among participants receiving the medication. “Just like in mice, they don’t have to lose weight or have altered glucose control to get this benefit,” he said.
Other studies, such as the PIONEER 2 trial, have shown large reductions in c-reactive protein levels (a marker of inflammation) without significant weight loss, he said.
Drucker also urged the field to acknowledge the medicines’ limitations. While some evidence suggests they can protect the brain, studies of their potential use for conditions such as Parkinson’s disease and Alzheimer’s disease have shown disappointing results.
Drucker called for more research on dose-response. He noted that pharmaceutical companies often favor testing maximum doses and have been reluctant to study lower-dose regimens, even though real world users frequently microdose. He pointed to the need for randomized trials that examine a full range of dosing.
“Not everyone needs to go to the highest dose, and not everyone needs the most expensive medications,” he said.
Between 75 and 100 GLP‑1–based medicines are currently in clinical development, including combination therapies aimed at improving efficacy. Drucker said the next phase of research must include not only basic science but clinical studies that identify better treatment options and improve access. He underscored the importance of equitable availability of these often-expensive medications.
Some of his current laboratory work, he added, is driven by real‑world patient reports, such as a person who experienced dramatic improvement in hand arthritis after a single GLP‑1 injection.
The lecture was the concluding event of the “Metabolism and Health Across the Lifespan,” research symposium, which featured talks from Duke University School of Medicine researchers.