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

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.

Long‐term morbidity and mortality in patients with Cushing's syndrome

“…Beyond anti‐diabetic use, there is evidence that the intake of metformin reduces other metabolic complications associated with glucocorticoid excess and affects low‐grade inflammation positively 16 . Additionally, metformin appears to have a positive effect on bone density; in patients with CS and those taking metformin, bone density is higher and levels of β‐isomerised C‐terminal telopeptides are decreased compared to matched patients with CS without metformin intake 17 …”

Whole genome sequencing resolves 10 years diagnostic odyssey in familiar myxoma

“…Metformin improves metabolic profiles of glucocorticoid-treated patients with inflammatory diseases 26 and has beneficial effects in patients with endogenous GC excess 27 . In addition, metformin is the most widely used oral antihyperglycemic agent, often used in polycystic ovary syndrome and its anticancer effects have been also reported 28 .…”

Metabolic regulation by biomaterials in osteoblast

“…Moreover, recent studies suggest that AMPK signaling may also be involved in the regulation of glucose metabolism in osteoblasts. AMPK activation in osteoblasts has been shown to increase glucose uptake and glycolysis, while inhibiting gluconeogenesis and has also been shown to regulate the expression of key genes involved in glucose metabolism, such as Glut1 and HK2 ( Vogel et al, 2021 ; J; Wei et al, 2015 ).Together, these studies suggest that AMPK signaling plays a crucial role in osteoblast function and bone formation, and that activation of AMPK in osteoblasts is important for bone nodule formation in vitro and the maintenance of bone mass in vivo further supporting a role for AMPK signaling in skeletal physiology.…”