Prevention of Metabolic Complications of Glucocorticoid Excess

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

According to current estimates, nearly 1% of the general population is treated with long-term glucocorticoids. Chronic hypercortisolism leads to a phenotype that resembles the metabolic syndrome. The investigators have shown that inhibition of adenosine-monophosphate-activated protein kinase (AMPK) activity in adipose tissue plays a role in corticosteroid-mediated insulin resistance. Metformin, one of the mainstay therapies for type 2 diabetes, is a known activator of AMPK, which mediates its beneficial effects on glucose and lipid metabolism. The investigators have shown in an animal model that metformin - via altering AMPK activity - prevents the development of the metabolic complications of glucocorticoid excess, and the investigators wish to confirm this in a human study. The aim of this prospective, randomised, double-blind, placebo-controlled study is to investigate the effect of metformin treatment on metabolic parameters in patients on long-term high-dose glucocorticoids. The study is part of the investigators translational project and could rapidly lead to immediate patient benefit, improving quality of life and reducing health care costs for the NHS.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Barts & The London NHS Trust
• Collaborator: Barts and the London School of Medicine and Dentistry
• Treatments: Glucocorticoids; Metformin

Criteria

Inclusion Criteria:

• patients diagnosed with an inflammatory condition and not started yet on GC treatment or • patients with an inflammatory condition treated with GC >20mg/d of prednisolone (or its cumulative equivalent) for at least 4wks

• minimal duration of prospective therapy 12w

• dose of prednisolone ≥10mg/d (or equivalent GC)

• ambulatory patients

• patients >18 years old

• ability to understand verbal and written instructions and informed consent

Exclusion Criteria:

• prior therapy with metformin during the last 6 months

• known pre-existing diabetes

• pregnancy

• breastfeeding

• liver impairment: ALT and/or AST ≥2.5 x UNL

• renal impairment: serum creatinine levels ≥135.0 µmol/L in males and ≥110.0 µmol/L in females

• current malignancy

• patients unable to give written informed consent

• or patients not understanding English