AUTHOR=Vogel Frederick , Braun Leah , Rubinstein German , Zopp Stephanie , Oßwald Andrea , Schilbach Katharina , Schmidmaier Ralf , Bidlingmaier Martin , Reincke Martin TITLE=Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study JOURNAL=Frontiers in Endocrinology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.765067 DOI=10.3389/fendo.2021.765067 ISSN=1664-2392 ABSTRACT=Context

Glucocorticoid 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.

Objective

To evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.

Patients and Methods

As 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.

Results

As 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.

Conclusion

This retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.