Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporosis. The effects of T2DM and anti-diabetic agents on bone and mineral metabolism have been observed. Sodium–glucose co-transporter 2 inhibitors (SGLT-2is) promote urinary glucose excretion, reduce blood glucose level, and improve the cardiovascular and diabetic nephropathy outcomes. In this review, we focused on the extraglycemic effect and physiological regulation of SGLT-2is on bone and mineral metabolism. SGLT-2is affect the bone turnover, microarchitecture, and bone strength indirectly. Clinical evidence of a meta-analysis showed that SGLT-2is might not increase the risk of bone fracture. The effect of SGLT-2is on bone fracture is controversial, and further investigation from a real-world study is needed. Based on its significant benefit on cardiovascular and chronic kidney disease (CKD) outcomes, SGLT-2is are an outstanding choice. Bone mineral density (BMD) and fracture risk evaluation should be considered for patients with a high risk of bone fracture.
Chronic kidney diseases (CKD) and cardiovascular diseases (CVD) are the main complications in type 2 diabetic mellitus (T2DM), increasing the risk of cardiovascular and all-cause mortality. Current therapeutic strategies that delay the progression of CKD and the development of CVD include angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA). In the progression of CKD and CVD, mineralocorticoid receptor (MR) overactivation leads to inflammation and fibrosis in the heart, kidney and vascular system, making mineralocorticoid receptor antagonists (MRAs) as a promising therapeutic option in T2DM with CKD and CVD. Finerenone is the third generation highly selective non-steroidal MRAs. It significantly reduces the risk of cardiovascular and renal complications. Finerenone also improves the cardiovascular-renal outcomes in T2DM patients with CKD and/or chronic heart failure (CHF). It is safer and more effective than the first- and second-generation MRAs due to its higher selectivity and specificity, resulting in a lower incidence of adverse effects including hyperkalemia, renal insufficiency and androgen-like effects. Finerenone shows potent effect on improving the outcomes of CHF, refractory hypertension, and diabetic nephropathy. Recently studies have shown that finerenone may have potential therapeutic effect on diabetic retinopathy, primary aldosteronism, atrial fibrillation, pulmonary hypertension and so on. In this review, we discuss the characteristics of finerenone, the new third-generation MRA, and compared with the first- and second-generation steroidal MRAs and other nonsteroidal MRAs. We also focus on its safety and efficacy of clinical application on CKD with T2DM patients. We hope to provide new insights for the clinical application and therapeutic prospect.
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