New research suggests that elevated cortisol may impair the effectiveness of GLP-1 incretin therapies in some patients, prompting calls for more nuanced diagnostic approaches to optimise diabetes treatment outcomes.
GLP-1 drugs have become best known for weight loss, but they were first developed for type 2 diabetes and remain important tools for many patients. In an interview with Pharmaceutical Executive, Elena Christofides, scientific and medical adviser for Sparrow Pharmaceuticals, argued that one reason some patients do not get the expected benefit is elevated cortisol, a hormone that can interfere with glucose control and insulin signalling.
Christofides said cortisol dysregulation can alter how the body handles fuel and blunt the effect of incretin therapies, the drug class that includes GLP-1 medicines. That matters because these treatments are often highly effective on average, but trial results do not always match what doctors see in practice. Healthline notes that GLP-1 receptor agonists can help lower blood sugar, support weight loss and improve cardiovascular outcomes, though common side effects such as nausea, vomiting and diarrhoea can affect adherence.
She also questioned the way cortisol is usually assessed. According to Christofides, a random cortisol or ACTH reading is not a useful screen, while 24-hour urine and salivary tests have narrower uses and can produce misleading results outside those settings. She said the overnight dexamethasone suppression test is the most meaningful way to check whether the hypothalamic-pituitary-adrenal axis is functioning properly, because a healthy system should suppress cortisol when given dexamethasone.
Her wider argument is that failure to respond to a GLP-1 should prompt a diagnostic review rather than an assumption that the patient is simply not following instructions. She said clinicians should consider cortisol problems earlier, particularly when patients remain above target despite treatment. That view fits a broader message in diabetes care: GLP-1 drugs are often used alongside medicines such as metformin or insulin, but no single therapy works equally well for every patient, and identifying the reason for poor response can be as important as choosing the drug itself.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
