Systematic Review and Meta-Analysis of the Metabolic Effects of Modified-Release Hydrocortisone versus Standard Glucocorticoid Replacement Therapy in Adults with Adrenal Insufficiency.

CONTEXT Published studies exploring the metabolic effects of Modified-Release Hydrocortisone (MR-HC) replacement in patients with adrenal insufficiency (AI). OBJECTIVE To compare metabolic effects of MR-HC with Standard Glucocorticoid (SG) replacement in adults with AI. Randomised control trials (RCTs) were meta-analysed; non-RCT studies described narratively with critical appraisal. DATA SOURCES PubMed/Medline, EMBASE, CINAHL and CENTRAL were searched to identify relevant articles, published before Aug 2019. STUDY SELECTION All study types that reported metabolic profile (including anthropometric, glucose and lipid-related parameters), on patients switched from SG to MR-HC replacement. Following independent screening from two reviewers, 390 studies were identified, of which 9 studies were included for review (RCT, n=2; non-RCT, n=7). DATA EXTRACTION Two independent reviewers assessed each paper for bias and data extraction. RESULTS Meta-analysis from RCTs (n=2), 104 patients were switched from SG to MR-HC replacement. Combining treatment effects, at 3-months post-therapy switch there was significant reduction in body weight (-0.82kg; 95% CI: -1.24kg to -0.40kg; p<0.001) and HbA1c (-0.13%; 95% CI: -0.214% to -0.045%; p=0.003). In the sub-group with Diabetes Mellitus (DM), reduction in HbA1C was more pronounced (-0.52%; 95% CI: -0.82% to -0.23%; p<0.001). Non-RCT studies showed improved anthropometric measures and glucose metabolism up to 48-months following switch from SG to MR-HC replacement. CONCLUSIONS In adults with AI, replacement with MR-HC associates with significant improvements in anthropometric measurements and HbA1c compared with SG replacement, particularly those with DM.