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. Randomized 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 (-0.82 kg; 95% CI: -1.24 kg to -0.40 kg; P < .001) and HbA1c (-0.13%; 95% CI: -0.214% to -0.045%; P = .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 < .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.