Glucose-Lowering Drugs and Fracture Risk—a Systematic Review

Abstract

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Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis

“…Among other anti-diabetic drugs evaluated, metformin, voglibose, and insulin showed benefits, whereas nateglinide raised the risk of fracture. Several recent studies have indicated that metformin is associated with a reduced risk of fracture ( 36 , 42 , 43 ), while previous studies have reported an increased risk of falling among patients using insulin ( 12 ). Therefore, metformin could be considered in patients susceptible to fracture.…”

Bone Density and Structure in Overweight Men With and Without Diabetes

“…Several drugs are used in the treatment for T2D, but only glitazone (which was not used by any of the participants in the present study) shows detrimental effects, whereas it is controversial whether other antidiabetic drugs influence fracture risk, bone density, or bone turnover ( 32 ). Metformin has in a randomized controlled trial been shown to reduce bone turnover markers ( 33 ), whereas observational studies in general report either beneficial or neutral effects of metformin on fractures or BMD ( 32 , 34 ). Sulfonylurea and insulin do not change bone turnover ( 32 , 35 ).…”

“…Sulfonylurea and insulin do not change bone turnover ( 32 , 35 ). The effect of these drugs on fracture risk is controversial as both drugs have been linked to an increased fracture risk through an increased risk of hypoglycemia, however, observational studies report neutral or even protective effects of the treatments ( 34 ). DPP-IV and GLP-1 receptor agonist have in preclinical studies shown bone formative effects ( 32 ), but observational and randomized controlled trials showed neutral effects on fracture risk ( 34 ).…”

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics

“…In our study, the mice in the liraglutide treatment groups suffered greater weight loss than the T1D mice which might cause negative effect on bone, which might partly explain the only partial improvement of bone microarchitectures. Metformin was also found to have an effect on bone metabolism, which was also mainly associated with neutral outcomes or decreased fracture risk in comparison to treatment with other glucose-lowering drugs ( 10 ). Metformin was found to decrease ALP, CTX-1, TRACP 5b, PINP, and RANKL, but increase OPG, RUNX2, and OPG/RANKL ratio in diabetic rat, indicating a bone protection role ( 40 ), but it was not exactly the same as liraglutide.…”

“…GLP-1R agonists also exert protective effects on bone tissue in vitro and in vivo (7)(8)(9). Some clinical studies have found neutral effects of liragutide on bone, but there was also a few meta-analysis of 16-59 randomized controlled trials with 11,206-49,602 patients with T2DM which showed that compared with placebo and other antidiabetic drugs, liraglutide was associated with a significant reduction in the risk of bone fractures (10)(11)(12)(13). However, clinical and experimental research data in the context of T1D are scarce.…”