GLP-1 Drugs in Cushing's Syndrome: Weight Down, Cortisol Unchanged

In Cushing’s syndrome the obesity and the diabetes are consequences of cortisol excess, which makes the obvious question a nervous one: does a drug that changes metabolism disturb the hormonal picture, or the monitoring that depends on it? A multicenter retrospective study of 20 adults with biochemically confirmed Cushing’s found weight down 10.3 kg and HbA1c down 0.5% over a median 13 months, with ACTH and cortisol levels unchanged.^[1] Twenty people is twenty people. But before this, the paper notes, the question was unexplored.

What was measured

Twenty adults with biochemically confirmed Cushing’s syndrome and concurrent type 2 diabetes and/or obesity, treated with a GLP‑1 receptor agonist — liraglutide, semaglutide, tirzepatide or dulaglutide — for at least three months. Anthropometric, hemodynamic, metabolic, hepatic and hormonal parameters were compared before and after therapy. Median follow-up was 13 months.^[1]

Mild gastrointestinal side effects were reported in 26.3% of patients, and the drugs were described as generally well tolerated.^[1]

What twenty retrospective patients cannot tell you

• There is no control group. Some of the weight and glucose change may reflect other treatment of the underlying Cushing's, which is what people with this condition are receiving.
• It is retrospective, so it reports what happened to be recorded rather than what was planned to be measured.
• Four different drugs are pooled into one group of twenty. Nothing here separates them.
• The blood pressure and lipid results showed no significant change, which is worth noting in a condition where both are commonly deranged.
• ⚠ Cushing's syndrome is managed by endocrinologists for good reason. This is information to bring to that conversation, not to act on alone.

And acromegaly, where there is nothing

Acromegaly is routinely bracketed with Cushing’s when this question comes up, both being pituitary-driven disorders with metabolic consequences. We looked and could not find a cohort or case series reporting GLP‑1 outcomes in acromegaly. Rather than let the Cushing’s result stand in for both, we are saying plainly that on acromegaly this register has nothing to report.