Beyond GLP-1: The Biological Case for Dual Incretin Therapy in MASH

In this episode, 'Beyond GLP-1: The Biological Case for Dual Incretin Therapy in MASH,' Nadege Gunn, MD explores the following question:

What is the biological rationale for a dual GLP-1/glucagon receptor agonist over a GLP-1 receptor agonist alone in patients with MASH?

Gunn explained the scientific rationale for combining GLP-1 and glucagon receptor agonism in the context of MASH, noting that the liver contains glucagon receptors, making the combination a compelling strategy for achieving more direct hepatic targeting than GLP-1 receptor agonism alone can provide. She highlighted that while GLP-1 receptor agonists have demonstrated meaningful benefits in weight reduction and some degree of hepatic fat reduction, the addition of glucagon receptor agonism raises the important question of whether a dual incretin approach could produce even greater and more liver-specific activity. Gunn further framed this as an area of significant scientific interest and opportunity, emphasizing that the goal of combining these incretin pathways is not simply to achieve more weight loss, but to determine whether a more targeted hepatic effect could meaningfully address the progressive liver disease that defines MASH.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

The next episode in this series, 'SYNCHRONIZE-1 Through a Hepatologist's Lens: Liver Fat Reduction, Visceral Fat, and What Comes Next,' features Nadege Gunn advancing her conversation on obesity and MASH and focusing on her interpretation of the SYNCHRONIZE-1 trial data.