Sulfonylureas and risk of falls and fractures among nursing home residents with type 2 diabetes mellitus

Lapane, Kate L.; Jesdale, Bill M.; Dubé, Catherine; Pimentel, Camilla B; Rajpathak, Swapnil

doi:10.1016/j.diabres.2015.05.009

Cited by 37 publications

(34 citation statements)

References 32 publications

(30 reference statements)

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“…A review in 2013 concluded that there was a lack of evidence for increased fracture risk with sulfonylurea use but that higher quality studies in older adults were needed to definitively address this question [69]. Since then, additional observational studies have reported on sulfonylureas and fracture risk with some [70][71][72], but not others [41, [73][74][75], reporting increased risk. In contrast, some [41, 74,76], although not all [70,73,77], observational studies of metformin and fracture risk have reported reduced fracture risk.…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Diabetes, bone and glucose-lowering agents: clinical outcomes

Schwartz

2017

Diabetologia

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Older adults with diabetes are at higher risk of fracture and of complications resulting from a fracture. Hence, fracture risk reduction is an important goal in diabetes management. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Beata Lecka-Czernik (DOI 10.1007/s00125-017-4269-4). Specifically, this review discusses the challenges of accurate fracture risk assessment in diabetes. Standard tools for risk assessment can be used to predict fracture but clinicians need to be aware of the tendency for the bone mineral density Tscore and the fracture risk assessment tool (FRAX) to underestimate risk in those with diabetes. Diabetes duration, complications and poor glycaemic control are useful clinical markers of increased fracture risk. Glucose-lowering agents may also affect fracture risk, independent of their effects on glycaemic control, as seen with the negative skeletal effects of the thiazolidinediones; in this review, the potential effects of glucose-lowering medications on fracture risk are discussed. Finally, the current understanding of effective fracture prevention in older adults with diabetes is reviewed.

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Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Diabetes, bone and glucose-lowering agents: clinical outcomes

Schwartz

2017

Diabetologia

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“…However, regarding bone integrity, one BMD remained stable from baseline following 52 or 104 weeks of treatment with either of these medications 252. The risk of fracture from SUs has, to date, predominately been associated with the risk of falls due to hypoglycemia[253][254][255][256] with SU therapy, and not to a direct effect of the drugs on bone remodeling (bone turnover markers) or integrity (ie, BMD) 252,257. Because SUs increase both first and second phase insulin release by β-cells (in a glycaemia-independent manner), hypoglycemia is a known risk factor of the SUs.…”

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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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“…A meta‐analysis showed that dementia risk was increased for underweight (BMI <18.5–20 kg/m 2 ) as well as obesity (BMI ≥30 kg/m 2 ) . Furthermore, the BMI (20.1 ± 3.6 kg/m 2 ) in the present patients was much lower than that in European people (average BMI, more than approximately 25 kg/m 2 ), and approximately half our patients were below the cut‐off level for malnutrition according to the Global Leadership Initiative on Malnutrition criteria (<20 kg/m 2 ) . Therefore, medical professionals should pay attention to underweight in Asian diabetes patients in nursing homes.…”

Section: Discussionmentioning

confidence: 47%

“…This might be because the use of DPP‐4i instead of sulfonylurea drugs is more common in Japan, and insulin use was lower compared with other countries. In fact, the present study showed DPP‐4i was used in 67.6% of residents among those using any antidiabetic medicines in Japanese nursing homes, whereas its use is rare in other countries . A recent randomized controlled study showed that treatment with linagliptin, a DPP‐4i, resulted in a significantly lower risk of hypoglycemia and non‐inferior glycemic control compared with insulin glargine in nursing facilities in the USA …”

Section: Discussionmentioning

confidence: 67%

“…According to Davis et al ., in nursing home residents using insulin, hypoglycemia was most frequent with HbA1c <7.0%, and falls increased in both groups with HbA1c <7.0% and >9.0% . In addition, residents with diabetes taking sulfonylureas or insulin were more likely to be associated with a high incidence of ADL disability and falls than those not taking these medications . However, these associations have not been reported among nursing home residents in Japan.…”

Section: Introductionmentioning

confidence: 90%

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Low hemoglobin A1c and low body mass index are associated with dementia and activities of daily living disability among Japanese nursing home residents with diabetes

Hatano

Araki

Ishibashi

2019

Geriatrics Gerontology Int

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Aim: To investigate associations between glycemic control and dementia, activities of daily living (ADL), falls and fractures in Japanese older adults with type 2 diabetes mellitus living in nursing homes.Methods: A total of 384 older residents with diabetes aged ≥65 years from 95 out of 132 facilities in Hiroshima Prefecture were studied in a cross-sectional study in 2016. Primary outcomes were differences in severity of dementia and ADL among three glycosylated hemoglobin level groups. Secondary end-points included differences in falls, fragility fracture and severe hypoglycemia.Results: Approximately 67.6% of patients receiving any diabetes treatment received dipeptidyl peptidase-4 inhibitors, and 26.0% received sulfonylureas. Patients with glycosylated hemoglobin <7.0% had a significantly higher severity of dementia compared with those with glycosylated hemoglobin 7.0-7.9% (beta AE SE, 0.55 AE 0.26; 95% CI 0.04-1.06) in multivariable ordinal logistic regression analysis. This tendency was observed particularly in patients using insulin (1.91 AE 0.91; 95% CI 0.13-3.69) or both sulfonylureas and dipeptidyl peptidase 4 (2.14 AE 0.88; 95% CI 0.41-3.87). Low body mass index was significantly associated with dementia (−0.08 AE 0.03; 95% CI −0.14 -−0.03) and ADL impairment (−0.15 AE 0.03; 95% CI −0.20 -−0.09), and fractures (odds ratio OR 0.89 per kg/m 2 ; 95% CI 0.84-0.96).Conclusions: Tight glycemic control was related to dementia in residents treated with insulin and sulfonylureas, and low body mass index was associated with dementia, ADL disability and fractures. Optimization of glycemic control and weight for people with diabetes in longterm care facilities could be important for the maintenance of cognitive and physical function.

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Sulfonylureas and risk of falls and fractures among nursing home residents with type 2 diabetes mellitus

Cited by 37 publications

References 32 publications

Diabetes, bone and glucose-lowering agents: clinical outcomes

Diabetes, bone and glucose-lowering agents: clinical outcomes

Diabetes pharmacotherapy and effects on the musculoskeletal system

Low hemoglobin A1c and low body mass index are associated with dementia and activities of daily living disability among Japanese nursing home residents with diabetes

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