Metformin; an old antidiabetic drug with new potentials in bone disorders

Bahrambeigi, Saman; Yousefi, Bahman; Rahimi, Mahdi; Shafiei‐Irannejad, Vahid

doi:10.1016/j.biopha.2018.11.032

Cited by 93 publications

(75 citation statements)

References 169 publications

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“…When compared with metformin, sulfonylureas increased the incidence of fracture by almost 25%. As a AMPactivatedproteinkinase agonist, metformin can inhibit the differentiation of mesenchymal stem cells toward adipocytes and decrease the incidence of fracture [25]. Therefore, it is possible that the apparent increased risk of fracture among sulfonylureas users might, indeed, from the protective effect of the metformin rather than from the detrimental effect of sulfonylureas.…”

Section: Discussionmentioning

confidence: 99%

“…Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues may have beneficial effect on bone in patients with diabetes by increasing the serum level of GLP-1 [23,24]. Metformin can decrease the fracture risk in patients and its potential mechanism maybe the inhibition of mesenchymal stem cells differentiating to adipocyte in bone marrow [25]. Sulfonylurea, as a widely used hopoglycemic agent, its influence on fracture is still controversial.…”

Section: Introductionmentioning

confidence: 99%

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Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

Zhang

Cao

Tao

et al. 2020

Diabetes Research and Clinical Practice

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

Zhang

Cao

Tao

et al. 2020

Diabetes Research and Clinical Practice

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“…As shown in Table 1, the activation of AMPK ultimately leads to increased catabolism by increasing cellular glucose uptake, fatty acid oxidation, and decreased glycogen synthesis while decreasing anabolism by reducing fatty acid, protein, and cholesterol synthesis [11,29,33]. Any activity that requires energy will tend to activate the AMPK pathway.…”

Section: Ampk and Osteogenesismentioning

confidence: 99%

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

Aung¹,

Amin²,

Gulraiz³

et al. 2020

Cureus

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As a worldwide aging population is on the rise, osteoporosis (OS) is becoming a global health burden. Therefore, many researchers and health authorities are looking into the potential prevention and treatment of OS. Although previously regarded as two separate pathological processes, diabetes (DM) and OS are now regarded as two conditions that can occur together. It is now believed that OS can develop as a complication of DM. This relationship is further evidenced through a reduction in bone mineral density in type-1 diabetes with a resulting increased risk of fracture. Although bone mineral density in type-2 diabetes mellitus is normal or increased, there is also increased fragility due to decreased bone quality. These abnormal bone qualities tend to occur through the production of reduced bone microvasculature and advanced glycation end product, AGE. Interestingly, one of the most common treatments for DM, metformin (MF), shows a promising result on the protection of diabetes and non-diabetes related bone turnover. It is believed that MF modulates its effect through the adenosine monophosphate-activated protein kinase (AMPK) pathway. Recent data regarded AMPK as a vital mediator of homeostasis. It is involved not only in glucose metabolism but also in osteogenesis. AMPK can directly influence the production of mature and good quality bone by decreasing osteoclasts, increasing osteoblast formation, and enhancing bone mineral deposition. As an activator of AMPK, MF also upregulates osteogenesis. Furthermore, MF can influence osteogenesis through a non-AMPK pathway, such as the fructose 1-6 phosphatase pathway, by reducing glucose levels. While already recognized as a safe and effective treatment for DM, this article discusses whether MF can be used for the prevention and treatment of OS.

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“…Recent studies have shown that some antidiabetic medications, namely metformin and sulfonylureas, have a positive effect on bone health and may potentially lower fracture incidence in patients with T2DM 20 21. Hence, antidiabetic medications can be used as a potential treatment strategy for T2DM bone disease without having to introduce new medications into patients’ treatment plans.…”

Section: Introductionmentioning

confidence: 99%

Antidiabetic and antiosteoporotic pharmacotherapies for prevention and treatment of type 2 diabetes-induced bone disease: protocol for two network meta-analyses

et al. 2020

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IntroductionPatients with type 2 diabetes mellitus (T2DM) are at risk for a variety of severe debilitating effects. One of the most serious complications experienced by patients with T2DM are skeletal diseases caused by changes in the bone microenvironment. As a result, patients with T2DM are at risk for higher prevalence of fragility fractures. There are a variety of treatments available for counteracting this effect. Some antidiabetic medications, such as metformin, have been shown to have a positive effect on bone health without the addition of additional drugs into patients’ treatment plans. Chinese randomised controlled trial (RCT) studies have also proposed antiosteoporotic pharmacotherapies as a viable alternative treatment strategy. Previous network meta-analyses (NMAs) and meta-analyses regarding this topic did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a two-part NMA that incorporates all available RCT data to provide the most comprehensive ranking of antidiabetics (part I) and antiosteoporotic (part II) pharmacotherapies in terms of their ability to decrease fracture incidences, increase bone mineral density (BMD) and improve indications of bone turnover markers (BTMs) in adult patients with T2DM.Methods and analysisWe will search Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Chinese literature sources (China National Knowledge Infrastructure, Chongqing VIP Information, Wanfang Data, Wanfang Med Online) for RCTs, which fit our criteria. We will include adult patients with T2DM who have taken antidiabetics (part I) or antiosteoporotic (part II) therapies with relevant outcome measures in our study. We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias will be evaluated in duplicate for each study, and the quality of evidence will be examined using Confidence in Network Meta-Analysis in accordance to the Grading of Recommendations Assessment, Development and Evaluation framework. We will use R and gemtc to perform the NMA. We will report changes in BMD and BTMs in either weighted or standardised mean difference, and we will report fracture incidences as ORs. We will use the Surface Under the Cumulative Ranking Curve scores to provide numerical estimates of the rankings of interventions.Ethics and disseminationThe study will not require ethics approval. The findings of the two-part NMA will be disseminated in peer-reviewed journals and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of T2DM bone disease. Our analysis should be able to provide physicians and patients with up-to-date recommendations for antidiabetic medications and antiosteoporotic pharmacotherapies for maintaining bone health in patients with T2DM.PROSPERO registration numberCRD42019139320.

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Metformin; an old antidiabetic drug with new potentials in bone disorders

Cited by 93 publications

References 169 publications

Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

Antidiabetic and antiosteoporotic pharmacotherapies for prevention and treatment of type 2 diabetes-induced bone disease: protocol for two network meta-analyses

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