The Future of Incretin Therapy with Jennifer Green, MD

At the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, HCPLive sat down with Jennifer Green, MD, professor of medicine at the Duke University School of Medicine, to discuss her presentation on the past and future of incretin-based therapy in diabetes and beyond.

Incretin therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists have long been used in treating obesity and diabetes. However, many modern incretin-based medications have been adapted to a variety of comorbidities, including sleep apnea, heart failure, osteoarthritis, and metabolic liver disease.1

Green suggested that these treatments may even be effective in treating Alzheimer’s and Parkinson’s, among other neurodegenerative diseases.

“When we think about the CNS effects of the incretin-based therapies, the GLP-1 based therapies, we tend to think most about the way that these agents can suppress appetite, but their effects may be much more broad than that,” Green told HCPLive. “So it is thought, for example, that our body’s own GLP-1 can reduce inflammation in the brain, and in fact might stimulate neurogenesis.”

Green also expressed interest in the recently conducted SURMOUNT-OSA trial examining tirzepatide’s efficacy in treating sleep apnea.

“SURMOUNT-OSA showed that, in individuals randomized to active tirzepatide therapy, at the end of the study almost half of them didn’t even have sleep apnea anymore, which is really incredible: you’re fundamentally addressing and perhaps eliminating an entire disease state,” Green said. “And within the spectrum of metabolic diseases, I would say that’s exceptionally rare.”

Although trials are ongoing to investigate the efficacy of incretin-based therapies in treating other diseases, Green acknowledged the potential roadblocks to such studies, indicating that they are still in early stages.

“For example, if a person is enrolled in a trial of a weight loss medication that they know has the potential to result in very dramatic weight loss, but they’re randomized to a placebo, it might be easy for the participants to become unblinded,” Green said. “If half of the patients are losing a tremendous amount of body weight and the other half are not, we might inadvertently or unintentionally break the blind of a trial, which is a major trial conduct issue.”

Green explained that managing patient expectations is a major challenge in testing incretin-based therapies across the board. Each patient enrolled in these trials is hoping to receive the active drug; if they discover that they have been given placebo, Green believes there is a danger that they will drop out of the trials. Green suggested an alternative method of comparing newly developed incretin-based therapies to existing medications in the form of active controls to avoid this clinical disruption.

Given the speed at which investigations into incretin-based therapies are being adopted, Green stresses the importance of remaining informed and adapting clinical practices to include newly discovered treatments and processes.

“I think it’s important to stay abreast of the literature, because there’s just more and more information becoming available every month that we need to understand and incorporate into our clinical practice,” Green told HCPLive.

Green reports the following disclosures: Boehringer Ingelheim, Lilly, Merck, NovoNordisk, AstraZeneca, Merck, and others

References

1. Green J. Incretins: Today and Tomorrow. Presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.