Cortisol and Type 2 Diabetes: Managing Cortisol

In the fifth episode of our insights series, Cortisol and Type 2 Diabetes: What Patients Need to Know, John Buse, M.D., Ph.D., addresses the practicalities of treating cortisol issues when they contribute to poor glucose control. Buse begins by clarifying that "lowering cortisol" is not exactly the right terminology. Instead, the correct clinical approach is to use direct therapies that intentionally interfere with either cortisol action or cortisol production. While a variety of drugs have traditionally been used to manage the very high cortisol levels caused by pituitary-based, ACTH-producing tumors in Cushing's syndrome, the milder form of hypercortisolism seen in patients with poorly controlled diabetes and resistant hypertension has primarily been evaluated using a single therapy: mifepristone.

The episode provides an inside look at how this medication is managed and titrated in a clinical setting. Mifepristone is available as a 300 milligram tablet, and in the clinical trial, patients were typically started on 300 milligrams a day. However, Buse notes that clinicians who are highly practiced in this therapy will sometimes start patients even more slowly, at just one or two tablets a week, to minimize the degree and extent of cortisol withdrawal syndrome. From there, the standard trial protocol involves stepping up from 300 milligrams once a day to 600 milligrams once a day after four weeks, and increasing to 900 milligrams a day after an additional four weeks if clinically necessary. While alternative cortisol-directed agents exist, Buse frankly shares that as a diabetologist, he has less personal experience with them because they have not been thoroughly demonstrated or widely utilized in this specific patient population.

Buse sheds light on why cortisol-directed therapies have historically lagged behind the highly evolved blood pressure and diabetes medications developed over the last twenty years. Because severe hypercortisolism was long categorized as a rare disease, the medical community faced limited opportunities to study these treatments on a larger scale. Fortunately, the landscape is shifting dramatically. The episode concludes with a message of hope, highlighting a current explosion of interest within the pharmaceutical industry. Ongoing clinical trials and novel agents are actively investigating whether these advanced, cortisol-directed therapies can successfully optimize both blood sugar and blood pressure control for individuals facing the daily challenges of resistant hypertension and difficult-to-control type 2 diabetes.