Targeting Iatrogenic Cushing’s Syndrome with 11β-hydroxysteroid dehydrogenase type 1 Inhibition

OVERVIEW

TICSI evaluated whether AZD4017, an 11ß-HSD1 inhibitor, could reduce glucocorticoid-associated side effects on blood pressure, blood glucose levels, bone, and lipid metabolism in healthy men.

DESIGN

Randomised, double-blind, placebo-controlled trial comparing the effects of AZD4017 with a placebo (dummy pill), when administered together with prednisolone (a glucocorticoid) for 7 days.

RESULTS

32 participants were randomised; 30 completed the trial per protocol and were included in the analysis.

The primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinaemic, normoglycaemic clamp) was not met. Over a 7-day period, investigators showed that AZD4017 significantly improved the adverse effects of prednisolone on levels of blood glucose and lipids, bone health, and blood pressure compared with placebo. Importantly, many of the desirable, anti-inflammatory actions of prednisolone were retained.

In conclusion, co-administration of AZD4017 with prednisolone in men is a potential strategy to limit its adverse glucocorticoid effects.

The full published article can be viewed here.