Kevin Peterson, MD, MPH: Incretin Therapy's Potential

At the end of 2023, the HCPLive Editorial Advisory Board was surveyed on the question, “In 10 years, what will we remember as the biggest story in medicine from 2023?”

Surprising few, the board primarily voted for the progression of GLP-1 receptor agonists—from promising metabolic agents to revolutionary treatments in obesity management.¹ Over the span of the last 5 years, indications for GLP-1 receptor agonists including semaglutide (Ozempic) have progressed from type 2 diabetes, to cardiovascular event risk reduction, to renal outcomes and now, to clinical weight reduction.² In the same time, agents have advanced to late-stage trials for the potential treatment of renal, hepatic and gastric outcomes.

Incretin therapies are, to paraphrase the advisory board, the biggest story in medicine. And that doesn’t appear to be changing anytime soon.

In an interview with HCPLive during the American Academy of Physician Associates (AAPA) 2024 Conference & Expo in Houston, TX, this week, Kevin Peterson, MD, MPH, professor in the department of family medicine and community health at the University of Minnesota and vice president of the American Diabetes Association (ADA), discussed his expert outlook on the much-celebrated drug class.

“The incretins are going to, I think, change the whole paradigm of the way we treat diabetes,” Peterson said. “We've really began to redefine weight management and obesity as a separate medical problem, and the incretins give us one of the first capabilities of addressing that effectively.”

Peterson noted the drug class has the potential to change the scale of concern placed on obesity and weight management strategies—especially given the proven clinical efficacy in reducing risk of comorbid cardiovascular events or metabolic diseases.

“ I think that's one of the impacts of the incretins is that it addresses obesity, and so it has a multifactorial set of diseases that it treats: cardiovascular disease, diabetes, even depression,” Peterson said. “I think it'll redefine our paradigm of treatment of weight in the primary care setting.“

While semaglutide and other incretin therapies are being largely celebrated for their weight management benefit, more novel clinical pursuits with the drug class are being considered. HCPLive has recently covered considerations to treat psychiatric conditions including depression and addiction,³ as well as hematologic and even gastric outcomes.^4,5

Peterson said this expansion of clinical research with the drug class may be due to the mechanism of action: GLP-1 receptor agonists target both the gut and brain, he explained.

“It delays gastric emptying, it reduces gluconeogenesis following meals from the liver, or at least excretion of glucose from the liver,” Peterson said. “Most people would say that the weight loss is predominantly an effect in your brain, but it certainly slows gastric emptying, it increases satiety. It kind of provides that ileal break that may not exist so much in people.”

As a third generation of the GLP-1 receptor agonist drug class—nearing 30 unique investigative agents—is currently in development, Peterson prospects that the effect of the drug class will only be amplified by its strategic pairing with hormonal agents.

“Depending on how you mix and match some of these gastrointestinal hormones, they have substantial and complementary effect,” he said. “So, it's going to be an interesting next few years. I don't know where it's going to stop, but it's I think that it's it's very effective and it's going to become more effective.”

References

1. ^{Kunzmann K. The 6 Biggest Stories in Medicine in 2023. HCPLive. Published December 1, 2023. https://www.hcplive.com/view/6-biggest-stories-medicine-2023}
2. ^{Campbell P. Semaglutide: The Drug of Today and a Steppingstone to Tomorrow. HCPLive. Published December 6, 2023. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow}
3. ^{Kunzmann K. Roger S. McIntyre, MD: GLP-1 Agonists for Psychiatry? HCPLive. Published May 5, 2024. https://www.hcplive.com/view/roger-mcintyre-md-glp-1-agonists-for-psychiatry}
4. ^{Iapoce C. SGLT2 Inhibitor Use Lowers Anemia Risk in Patients with Diabetes, CKD. HCPLive. Published March 5, 2024. https://www.hcplive.com/view/sglt2-inhibitor-use-lowers-anemia-risk-patients-diabetes-ckd}
5. ^{Iapoce C. SGLT2is, GLP-1s Display Reno-Protective Benefit in Sickle Cell Disease. HCPLive. Published April 28, 2024. https://www.hcplive.com/view/sglt2is-glp-1s-display-reno-protective-benefit-sickle-cell-disease}