The aim of the present studies was to design a once weekly GLP-1 analogue by increasing albumin affinity and secure full stability against metabolic degradation. Studies have found that GLP-1RAs and their analogs have the effect of alleviating diabetic osteoporosis (Mabilleau et al., 2018). The physiological role of GLP-1 mainly regulates glucose levels by stimulating the secretion of insulin, inhibiting the secretion of glucagon and regulating gastric emptying, thereby enhancing bone formation (Hare et al., 2009). ApoE−/− mice are mainly used to study atherosclerosis, but ApoE−/− mice can also be used to study osteoporosis. There is still a lack of clinical studies on the efficacy of GLP-1RAs in patients with osteoporosis. GLP-1RAs for the prevention of osteoporosis and fracture are controversial. Between 1960 and 2010, the prevalence of adult obesity in the United States nearly tripled, to 36 percent from 13 percent, according to the Centers for Disease Control and Prevention. Furthermore, the relative importance of endogenous GLP-2 versus GLP-1 or glucagon as orchestrators of these chemogenetic responses was not determined and ColonBroom nutrition is clearly less important for weight control relative to pharmacological actions of the same peptides. Bottom right, the central polar network is stabilized by a distinct network of structural waters relative to peptide-mediated activation.

AGEs receptor (RAGE) is expressed in human osteoclasts and stimulates the activation of nuclear factor Kappa-B in osteoclasts, thereby increasing the production of cytokines and reactive oxygen species. The continuous accumulation of pro-inflammatory cytokines and reactive oxygen species will break the balance between osteoclasts and osteoblasts, increase the differentiation of osteoclasts, and lead to bone loss. Another study showed that GLP-1RA of liraglutide and exenatide can increase bone mass, structural parameters and connectivity in ovariectomized mice (Pereira et al., 2015). Montes Castillo et al. It operates across various regulatory programs within the EPA, reflecting a broader framework for ensuring the quality and reliability of nonclinical study data used in regulatory decision-making. A cohort study showed that there was no decreased risk of fracture with current use of GLP-1RA (sexenatide and liraglutide) compared to never-GLP-1RAs use. GLP-1RAS use did not significantly reduce the risk of osteoporotic fractures. Therefore, we believe that patients with T1DM and T2DM are closely related to osteoporosis and fractures.

2019) found that postprandial GLP-1 levels are related to osteoporosis risk in non-diabetic postmenopausal women. The result showed that the use of GLP-1RAs could significantly reduce the risk of fracture in patients, and the beneficial effect depends on the duration of treatment (Cheng et al., 2019). In our previous study, we analyzed 54 eligible random control trials treated with GLP-1RAs. Glucocorticoid (GC) treatment is the main cause of secondary osteoporosis. Therefore, it is controversial whether GLP-1RAs therapy could prevent and treat diabetic osteoporosis and fragility fractures in clinical practice. In one study, liraglutide was used to treat streptozotocin (STZ)-induced diabetes and/or bilateral ovariectomy (OVX) rats for 8 weeks. In this 2 years prospective study, ColonBroom nutrition the researchers found that liraglutide monotherapy did not affect the patient’s total bone mineral density (Gilbert et al., 2016). But, a meta-analysis included 38 randomized controlled trials with 39,795 patients with T2DM. T2DM. The results showed that at 52 weeks or 104 weeks, patients with liraglutide (1.8 or 1.2 mg/day) or glimepiride (8 mg/day) had no significant difference in average total bone mass change compared with baseline. A 52 weeks, controlled trial, investigated the efficacy of GLP-1RAs of liraglutide (1.2 and 1.8 mg/day) vs.

In our laboratory, we investigated the protective effect of geniposide (GLP-1RA) in dexamethasone-induced osteogenic inhibition. GLP-1RAs may improve BMD, bone strength and bone microstructure and reversed GIOP, primarily through slow down of bone resorption and promotion of bone formation and osteogenic differentiation. The excess AGEs increases chronic inflammation and bone resorption in diabetics. The underlying mechanisms include changes in bone mechanical properties caused by non-enzymatic glycosylation, mineralization disorders, and bone micro-damages. Because, in a long-term state of hyperglycemia, the non-enzymatic glycosylation of proteins, phospholipids and nucleic acids will lead to the continuous formation and accumulation of AGE. The excess AGEs could lead to non-enzymatic cross-linking of collagen, break the adhesion of osteoblasts to the extracellular matrix and leads to bone fragility (Mohsin et al., 2019). These changes in the extracellular matrix also reduced the alkaline phosphatase activity in mature osteoblasts and affected bone mineralization. At present, clinical treatment is mainly through restricting the patient’s diet and regulating blood sugar, strengthening daily exercise and supplementing calcium and vitamins, and using bone formation promoters and bone loss inhibitors for comprehensive treatment.