GLP-1 Agonists and the Gut-Brain Axis: A New Era in Obesity Management

In January 2023, Robert Kushner, MD, MS, professor of medicine and medical education at Northwestern University Feinberg School of Medicine, and Ania Jastreboff, MD, PhD, professor of medicine and pediatrics at Yale School of Medicine, published a review of glucagon-like peptide 1 (GLP-1) receptor agonists and the future of nutrient-stimulated hormone-based antiobesity therapeutics.

This year, at the American Society for Preventive Cardiology (ASPC) 2024 Congress on CVD Prevention, Kushner presented on the “new era” of obesity management, emphasizing the therapeutic targeting of the gut-brain axis with GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)–mimicking hormones. According to Kushner, these advanced treatments not only facilitate significant weight loss, but also offer broader health benefits, such as improved cardiovascular outcomes and enhanced organ function.

Transcript

What are you focusing on in your ASPC Congress session on GLP-1 agonists for obesity management?

In my session, I'm going to be highlighting a major theme, and that is that we are at an inflection point regarding treatment of obesity, and I qualify the inflection point by 3 major areas. One is that we are shifting the therapeutic target of obesity—I actually call that a paradigm shift—and we're shifting it to the gut-brain axis, which we really haven't seen before. What we're doing now is mimicking the naturally occurring gut hormones, such as GLP-1 or GIP, and give them back as synthesized versions at hyperpharmacological levels to cause significant benefits. The second major area is that we have highly effective medications that are born out of these mimicking hormones, such as semaglutide or tirzepatide, again highly effective, more than we've seen before. And the last is that these incretin hormones like GLP-1 or GIP have pleiotropic effects, and that is beyond weight loss, they have effects in multiple organs of the body, which is improving the overall health of our patients that are living with obesity.

What are some major updates to the obesity management landscape you’ve seen in the past year, especially around nutrient-stimulated hormone-based antiobesity therapeutics?

Building off of these highly effective medications that have pleiotropic effects, what we're seeing now published in highly reputable journals which we haven't seen before—like New England Journal of Medicine, Lancet, and so forth—are the effects of these medications on reducing cardiovascular disease and outcomes; improving the symptoms of individuals with obstructive sleep apnea; improving kidney function in those with overweight, obesity, and diabetes; improving the risk of developing diabetes; and lastly, improving what we call now metabolic [dysfunction]–associated steatotic liver disease or MASLD. These are these weight-independent effects that are really involving the health of our patients that we treat and we're getting a lot of play and so many more articles, they're going to be coming out soon as well.