Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study.

Frederick Vogel,Katharina Schilbach,Leah Braun,Ralf Schmidmaier,German Rubinstein,Andrea Oßwald,Martin Reincke,Stephanie Zopp,Martin Bidlingmaier

doi:10.3389/fendo.2021.765067

Frederick Vogel, Katharina Schilbach + Show 7 more

Open Access

https://doi.org/10.3389/fendo.2021.765067

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Abstract

ContextGlucocorticoid excess exhibits multiple detrimental effects by its catabolic properties. Metformin was recently suggested to protect from adverse metabolic side-effects of glucocorticoid treatment. Whether metformin is beneficial in patients with endogenous glucocorticoid excess has not been clarified.ObjectiveTo evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.Patients and MethodsAs part of the German Cushing’s Registry we selected from our prospective cohort of 96 patients all 10 patients who had been on pre-existing metformin treatment at time of diagnosis (CS-MET). These 10 patients were matched for age, sex and BMI with 16 patients without metformin treatment (CS-NOMET). All patients had florid CS at time of diagnosis. We analyzed body composition, metabolic parameters, bone mineral density and bone remodeling markers, muscle function and quality of life.ResultsAs expected, diabetes was more prevalent in the CS-MET group, and HbA1c was higher. In terms of comorbidities and the degree of hypercortisolism, the two groups were comparable. We did not observe differences in terms of muscle function or body composition. In contrast, bone mineral density in metformin-treated patients was superior to the CS-NOMET group at time of diagnosis (median T-Score -0.8 versus -1.4, p = 0.030). CS-MET patients showed decreased β-CTX levels at baseline (p = 0.041), suggesting reduced bone resorption under metformin treatment during glucocorticoid excess.ConclusionThis retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.

Highlights

Metabolic side-effects of glucocorticoids (GC) are common and challenging in both endogenous and exogenous GC excess
Cushing’s syndrome (CS) is associated with poor quality of life, Metformin and Bone Metabolism in Hypercortisolism morbidity and increased mortality, even after successful surgery leading to biochemical remission [2,3,4]
Our results suggest that metformin has a beneficial effect on bone metabolism during endogenous hypercortisolism

Summary

Introduction

Metabolic side-effects of glucocorticoids (GC) are common and challenging in both endogenous and exogenous GC excess. In a recently published study, Pernicova et al [5] reported that metformin administration improved metabolic profiles of glucocorticoid-treated patients with inflammatory diseases in a randomized, double-blind, placebo-controlled, phase 2 clinical trial. Whether metformin has beneficial effects in patients with endogenous GC excess is largely unknown. The mechanisms of action are still not fully understood The aim of this retrospective cohort study was to analyze the metabolic profile and bone turnover of patients with and without pre-existing metformin treatment at the time of endogenous GC excess. We hypothesized that standard metformin use is beneficial for bone metabolism in patients with florid CS

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