Sodium‐glucose cotransporter 2 (<scp>SGLT2</scp>) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

Ruanpeng, Darin; Ungprasert, Patompong; Sangtian, Jutarat; Harindhanavudhi, Tasma

doi:10.1002/dmrr.2903

Cited by 118 publications

(93 citation statements)

References 47 publications

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“…(1) More long‐term trials were included. The included trials ranged from 24 to 206 weeks, with an average of 64.22 weeks; thus, the duration of the trials included in this meta‐analysis was longer than that of the previous two studies (Ruanpeng et al 24 to 104 weeks, average 38 weeks and Tang et al 24 to 160 weeks, average 57.47 weeks). (2) This analysis was based on the latest research.…”

Section: Discussioncontrasting

confidence: 88%

“…Whether SGLT2 inhibitors give rise to a higher risk of bone fracture has received equal attention in clinical practice. Two previous meta‐analyses did not find a correlation between SGLT2 inhibitor therapy and a higher risk of fracture . Ruanpeng et al retrieved 20 studies on canagliflozin, dapagliflozin, and empagliflozin .…”

Section: Discussionmentioning

confidence: 99%

“…Two previous meta‐analyses did not find a correlation between SGLT2 inhibitor therapy and a higher risk of fracture . Ruanpeng et al retrieved 20 studies on canagliflozin, dapagliflozin, and empagliflozin . This study included 8286 patients from inception to November 2015 and did not observe an increased risk of bone fracture among patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

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Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis

Cheng

et al. 2019

Diabetes Metabolism Res

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Background The aim of the study is to update and determine the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor therapy on fracture and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). Methods We identified 27 eligible randomized controlled trials (RCTs) that compared the efficacy and safety of SGLT2 inhibitors to a placebo in 20 895 T2DM participants, with an average duration of 64.22 weeks. The relative risk (RR) of bone fracture and weighted mean difference (WMD) of changes in the BMD from baseline were determined to evaluate the risk of fracture. The degree of heterogeneity was evaluated by the I2 statistic, and publication bias was estimated using a funnel plot and Egger test. Results The pooled RR was 1.02 (95% CI [0.81, 1.28]) with low heterogeneity, indicating that SGLT2 inhibitor treatment was not correlated with a higher risk of fracture. Additionally, no increased risk was found for patients with different ages, sexes, and levels of HbA1c and some biochemical indicators. Three trials with 1303 patients reported a change in the BMD from baseline. SGLT2 inhibitor treatment did not decrease the BMD at four skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm), and the overall WMD was 0.08 (95% CI [−0.09, 0.26]). No significant publication bias was detected. Conclusions No increased risk for bone fracture was detected in patients with T2DM treated with SGLT2 inhibitors in this meta‐analysis. SGLT2 inhibitor therapy did not appear to affect bone health, but more long‐term detailed data are needed to validate this conclusion.

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Section: Discussioncontrasting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis

Cheng

et al. 2019

Diabetes Metabolism Res

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“…A recent meta-analysis of 20 SGLT2 inhibitor trials actually has not confirmed an increased risk of fractures with dapagliflozin, empagliflozin, or canagliflozin [41]. More data are necessary to understand the effect of these new medications on bone health.…”

Section: Impact Of Diabetes Medication On Fracture Riskmentioning

confidence: 99%

Diagnosis and management of bone fragility in diabetes: an emerging challenge

et al. 2018

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Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.

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“…Additionally, in patients with moderate renal impairment receiving dapagliflozin for 104 weeks, 7.7% of subjects experienced a bone fracture, compared with no fractures in the placebo group . In contrast, by cumulative meta‐analyses of randomized controlled trials, along with systematic literature review, several later publications have subsequently demonstrated that the incidence of skeletal fracture, compared with placebo, does not appear to be increased across the currently available SGLT2 inhibitor drugs when used for the treatment of T2D . However, it is also recognized that the duration of treatment, and duration of patient follow‐up for most of these studies remains relatively short for evaluating any treatment‐emergent effect on skeletal integrity and strength.…”

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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Sodium‐glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis

Abstract: Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta-analysis. However, the results were limited by short duration of treatment/follow-up and low incidence of the event of interest.

Cited by 118 publications

References 47 publications

Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis

Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis

Diagnosis and management of bone fragility in diabetes: an emerging challenge

Diabetes pharmacotherapy and effects on the musculoskeletal system

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