How Elevated Cortisol Levels Can Impact Type II Diabetes Treatments

GLP-1 medications might be most well-known as weight-loss options, but they were originally developed as a treatment for type 2 diabetes. For many patients, the drugs remain a highly effective treatment for the condition.

However, GLP-1s are not perfect and don’t work for every patient. In April of this year, Pharmaceutical Executive spoke with Mark Bagnall, CEO of Phenomix, discussed various reasons why a significant number of patients go off the medication within the first year of using it. His discussion focused on how side effects can be severe and incapitating, while the results can be inconsistent.

Pharmaceutical Executive recently spoke with Dr. Elena Christofides, scientific/medical advisor for Sparrow Pharmaceuticals, about a different issue some GLP-1 users face. Specifically, patients with high cortisol levels face unique challenges that GLP-1s may not be able to tackle.

Pharmaceutical Executive: How do elevated cortisol levels impact type II diabetes treatments?
Dr. Elena Christofides: The incretin class has produced genuinely remarkable medications — significant blockbusters in both diabetes and obesity — but the reality is they don't always work for everyone. Patients are not always achieving the responses that clinical trial data would lead us to expect. That raises an important question: why aren't people reaching their goals, or getting as much response as the average or mean would suggest?

Cortisol is a significant biological agent that controls virtually every system in the body. If a patient has cortisol dysrhythmia, they are not going to achieve the same degree of response in their diabetes or obesity management that the published clinical averages would predict. And epidemiologically, this is proving to affect a meaningful portion of the population — not a small subset.

The mechanism is direct: cortisol disrupts glucose signaling, insulin signaling, hormone integration, and fuel partitioning. If a patient has a cortisol problem, the drugs we assume to be most effective in managing diabetes and obesity will be less effective — and in many cases, ineffective. That makes identifying cortisol dysfunction a critical step in ensuring that the patients being treated with any given medication are actually part of the population that will respond to it. It also has significant implications for clinical trial design: if cortisol dysregulation is not accounted for in patient selection, the efficacy data that results will not reflect what these medications can actually achieve in appropriately selected patients.