Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

Mabilleau, Guillaume; Pereira, Marie; Chenu, Chantal

doi:10.1530/joe-17-0278

Cited by 34 publications

(36 citation statements)

References 117 publications

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“…The presence of the GLP-1 receptor on the pre-osteoblasts and osteocytes surface was associated with the anabolic actions of liraglutide and exenatide in murine models (90)(91)(92). In humans, exenatide and liraglutide treatment were found to prevent bone loss associated with weight reduction, and a 16% increase in P1NP serum levels was observed in liraglutide-treated patients (93,94).…”

Section: Incretinsmentioning

confidence: 99%

The Interplay Between Bone and Glucose Metabolism

et al. 2020

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The multiple endocrine functions of bone other than those related to mineral metabolism, such as regulation of insulin sensitivity, glucose homeostasis, and energy metabolism, have recently been discovered. In vitro and murine studies investigated the impact of several molecules derived from osteoblasts and osteocytes on glucose metabolism. In addition, the effect of glucose on bone cells suggested a mutual cross-talk between bone and glucose homeostasis. In humans, these mechanisms are the pivotal determinant of the skeletal fragility associated with both type 1 and type 2 diabetes. Metabolic abnormalities associated with diabetes, such as increase in adipose tissue, reduction of lean mass, effects of hyperglycemia per se, production of the advanced glycation end products, diabetes-associated chronic kidney disease, and perturbation of the calcium-PTH-vitamin D metabolism, are the main mechanisms involved. Finally, there have been multiple reports of antidiabetic drugs affecting the skeleton, with differences among basic and clinical research data, as well as of anti-osteoporosis medication influencing glucose metabolism. This review focuses on the aspects linking glucose and bone metabolism by offering insight into the most recent evidence in humans.

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Section: Incretinsmentioning

confidence: 99%

The Interplay Between Bone and Glucose Metabolism

et al. 2020

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“…No significant differences were observed between diabetic patients under treatment with (n = 35) or without (n = 125) TZDs, with (n = 10) or without (n = 150) SGLT-2 inhibitors, and with (n = 85) or without (n = 75) insulin in this study. Liraglutide and exenatide, two GLP-1 RAs, may improve skeletal blood supply, increase bone mineral density (BMD), and reduce the risk of osteoporosis and fracture in animal and human studies [27,50]. However, the bone protective effects behind this require clinical studies.…”

Section: Journal Of Diabetes Researchmentioning

confidence: 99%

Low Bone Turnover Markers in Young and Middle-Aged Male Patients with Type 2 Diabetes Mellitus

Liu

Jiang

Liu

et al. 2020

Journal of Diabetes Research

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Accumulating evidence has supported an increased risk of osteoporotic fracture in postmenopausal women and elderly men diagnosed with diabetes mellitus. However, it is not uncommon for young and middle-aged male patients diagnosed with type 2 diabetes mellitus (T2DM) to suffer from osteopenia or osteoporosis. Few studies focused on this population group are available. The aim of this study is to evaluate bone metabolic status and investigate the influence of T2DM on bone metabolism in 30-50-year-old men. Anthropometric assessment and blood samples were obtained from 160 patients with T2DM and 69 nondiabetic volunteers. Serum parathyroid hormone (PTH) and bone turnover markers (BTMs), including serum procollagen type I N-terminal peptide (PINP), osteocalcin (OC), and β-cross-linked C-telopeptide of type I collagen (β-CTX), were analysed. No significant differences were observed based on age, body mass index, systolic blood pressure, serum calcium, phosphorus, creatinine, total protein, and albumin levels when comparing T2DM and control groups. Fasting blood glucose, HbA1c, triglyceride (TG), total cholesterol, and low-density lipoprotein cholesterol were significantly increased, while high-density lipoprotein cholesterol was significantly decreased in the T2DM group. Compared with controls, diabetic patients showed lower serum PINP, OC, and PTH levels, whereas serum β-CTX levels were similar between the two groups. Moreover, HbA1c levels were positively correlated with PINP and inversely associated with PTH levels. TG levels were negatively correlated with OC or β-CTX levels. Furthermore, multiple linear regression revealed a positive correlation between HbA1c and PINP levels. These results also revealed a negative association between HbA1c and PTH, and between TG and OC levels, even after adjusting for expected confounder factors. Collectively, these findings indicated that young and middle-aged male patients with T2DM showed a lower turnover state resulting from bone formation inhibition. Glucose and lipid metabolic disorders may affect bone formation through different pathways.

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“…Liraglutide is another GLP‐1R agonist with delayed kidney clearance and considerably longer half‐life compared with GLP‐1 (t ½ = 11‐13 hours) that has been approved for use in T2D. GLP‐1 treatment has been associated with anabolic action on bone, and particularly, with increases in bone mass, improvement in the trabecular and cortical bone architecture, and enhancement of bone strength and is considered one of the most promising therapies for treating diabetes‐associated bone disease . Although there are number of studies evaluating the potential effects of exenatide and liraglutide on the skeleton, there is very little data on the skeletal effects of the other GLP‐1 agonists.…”

Section: Drugs and Bonementioning

confidence: 99%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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Summary Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age‐matched persons without diabetes, attributed to disease‐specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin‐based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall‐related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo‐anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium‐dependent glucose co‐transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes‐related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.

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Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

Cited by 34 publications

References 117 publications

The Interplay Between Bone and Glucose Metabolism

The Interplay Between Bone and Glucose Metabolism

Low Bone Turnover Markers in Young and Middle-Aged Male Patients with Type 2 Diabetes Mellitus

Diabetes pharmacotherapy and effects on the musculoskeletal system

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