Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis

Tsai, Wen-Hsuan; Kong, Siang-Ke; Lin, Chu-Lin; Cheng, Kai-Hsuan; Cheng, Yi-Ting; Chien, Ming-Nan; Lee, Chun-Chuan; Tsai, Ming-Chieh

doi:10.1016/j.diabres.2022.110082

Cited by 4 publications

(9 citation statements)

References 75 publications

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“…The authors reported an overall significant reduction in fracture risk in GLP-1RA-treated patients [72]. Similar results are described by the more recent network meta-analysis by Tsai et al, where the use of GLP-1RA demonstrated higher antifracture efficacy compared to placebo and other classes of drugs [71]. Similar data are not available in patients with T2DM and CKD.…”

Section: Clinical Studiessupporting

confidence: 75%

“…Similarly, an inverse relationship between metformin use and risk of fracture was described in a systematic review and meta-analysis of six observational studies [70]. A more recent network meta-analysis of 161 studies in a total of 191,361 patients treated with different classes of antidiabetics reported no influence of metformin on fracture risk [71].…”

Section: Clinical Studiesmentioning

confidence: 82%

“…Notwithstanding, a general conclusion of a substantial neutral effect on fracture risk of the SGLT-2i could be made. The negative effect on fracture observed in the Canagliflozin Cardiovascular Assessment Study (CANVAS) was not confirmed by other studies [71,84,85]. In a pooled analysis of CANVAS, Watts et al demonstrated that the incidence of fracture was significantly higher in the canagliflozin (4%) group compared to the placebo (2.6%) group [84].…”

Section: Clinical Studiesmentioning

confidence: 96%

“…A retrospective analysis of 200 patients with T2DM reported a similar BMD increase after 12 months in the DPP-4i and in the control group (treated with other classes of antidiabetics), and a trend toward a higher TBS value in the DPP-4i group [76]. Several meta-analyses were performed to explore the association between DPP-4i and fracture risk, including a vast number of RCTs performed in thousands of patients with almost all molecules of this class and compared with placebo or other antidiabetics [71,[77][78][79]. They collectively demonstrated that there is no significant association between DPP-4i use and fractures.…”

Section: Clinical Studiesmentioning

confidence: 99%

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Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes

Cipriani,

Lauriero,

Tripepi

et al. 2023

JCM

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Among the metabolic changes occurring during the course of type 2 diabetes (T2DM) and diabetic kidney disease (DKD), impaired bone health with consequent increased fracture risk is one of the most complex and multifactorial complications. In subjects with diabetic kidney disease, skeletal abnormalities may develop as a consequence of both conditions. In the attempt to define a holistic approach to diabetes, potential effects of various classes of antidiabetic drugs on the skeleton should be considered in the setting of normal kidney function and in DKD. We reviewed the main evidence on these specific topics. Experimental studies reported potential beneficial and harmful effects on bone by different antidiabetics, with few data available in DKD. Clinical studies specifically designed to evaluate skeletal effects of antidiabetics have not been performed; notwithstanding, data gleaned from randomized controlled trials and intervention studies did not completely confirm observations made by basic research. In the aggregate, evidence from meta-analyses of these studies suggests potential positive effects on fracture risk by metformin and glucagon-like peptide-1 receptor agonists, neutral effects by dipeptidyl peptidase-4 inhibitors, sodium–glucose cotransporter-2 inhibitors, and sulfonylureas, and negative effects by insulin and thiazolidinediones. As no clinical recommendations on the management of antidiabetic drugs currently include fracture risk assessment among the main goal of therapy, we propose an integrated approach with the aim of defining a patient-centered management of diabetes in chronic kidney disease (CKD) and non-CKD patients. Future clinical evidence on the skeletal effects of antidiabetics will help in optimizing the approach to a personalized and more effective therapy of diabetes.

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Section: Clinical Studiessupporting

confidence: 75%

Section: Clinical Studiesmentioning

confidence: 82%

Section: Clinical Studiesmentioning

confidence: 96%

Section: Clinical Studiesmentioning

confidence: 99%

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Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes

Cipriani,

Lauriero,

Tripepi

et al. 2023

JCM

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“…In addition to the direct effects of diabetes on bone fragility, current medical management of T2DM also substantially impacts bone health and fracture risk ( 22 , 23 ). For instance, thiazolidinediones have been associated with an increased fracture risk ( 24 , 25 ), whereas metformin administration has been shown to have a protective effect on the bone health of diabetic patients ( 24 – 26 ).…”

Section: Introductionmentioning

confidence: 99%

Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies

Yu¹,

Ye²,

Li³

et al. 2023

Front. Endocrinol.

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AimsIncreasing evidence suggests that metformin can affect bone metabolism beyond its hypoglycemic effects in diabetic patients. However, the effects of metformin on fracture risk in type 2 diabetes mellitus (T2DM) patients remain unclear. A systematic review and meta-analysis were performed in this study to evaluate the association between metformin application and fracture risk in T2DM patients based on previous studies published until June 2021.MethodsA systematic search was performed to collect publications on metformin application in T2DM patients based on PubMed, Embase, Cochran, and Web of Science databases. Meta-analysis was performed by using a random-effects model to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). Subgroup analyses based on cohort/case-control and ethnicity and sensitivity analyses were also performed.ResultsEleven studies were included in the meta-analysis. Results demonstrated metformin use was not significantly associated with a decreased risk of fracture (RR, 0.91; 95% CI, 0.81–1.02; I2 = 96.8%). Moreover, metformin use also demonstrated similar results in subgroup analyses of seven cohort studies and four case-control studies, respectively (RR, 0.90; 95% CI, 0.76–1.07; I2 = 98.0%; RR, 0.96; 96% CI, 0.89–1.03; I2 = 53.7%). Sensitivity analysis revealed that there was no publication bias.ConclusionThere was no significant correlation between fracture risk and metformin application in T2DM patients. Due to a limited number of existing studies, further research is needed to make a definite conclusion for clinical consensus.

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The relationship between use of SGLT2is and incidence of respiratory and infectious diseases and site-specific fractures: a meta-analysis based on 32 large RCTs

Wang,

Zhou

2024

Eur J Clin Pharmacol

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Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis

Cited by 4 publications

References 75 publications

Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes

Effect of Antidiabetic Drugs on Bone Health in Patients with Normal Renal Function and in Chronic Kidney Disease (CKD): Insight into Clinical Challenges in the Treatment of Type 2 Diabetes

Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies

The relationship between use of SGLT2is and incidence of respiratory and infectious diseases and site-specific fractures: a meta-analysis based on 32 large RCTs

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