Effects of gliflozins on bone health of patients with chronic kidney disease: a systematic review.
Mariana Cassani de Oliveira, Lorena Rufino, Ana Laura Mendes Lourenço et al.
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In 30 seconds
This systematic review assessed skeletal safety and bone-related metabolic outcomes with sodium-glucose co-transporter-2 inhibitors (SGLT2i) in people with chronic kidney disease, drawing on randomised trials and observational cohort studies. Findings were generally reassuring: fracture and amputation signals reported in one trial and one cohort were not consistently reproduced in other studies, which mostly found non-significant differences. One study suggested more favourable CKD-mineral bone disease markers with SGLT2i. The review notes that evidence largely came from studies designed for type 2 diabetes and early-stage CKD, leaving uncertainty in moderate-to-advanced CKD.
Key findings
- One randomised trial and one cohort study reported significantly increased fracture and amputation risk; subsequent trials and cohorts generally did not replicate these findings.
- One study associated SGLT2i use with lower risks of hyperphosphatemia, hypocalcemia, high parathyroid hormone, and low vitamin D.
- Bone-related outcomes were inconsistently reported, and much of the evidence involved early-stage CKD subgroups in studies primarily designed for type 2 diabetes.
Why it matters
Skeletal safety is relevant when considering SGLT2i in CKD, where bone and mineral abnormalities may already be a concern. The review offers some reassurance that fracture signals have not been consistent across studies, but the evidence does not settle safety in moderate-to-advanced CKD or establish long-term effects. Better-defined skeletal outcomes would help clarify these uncertainties.
What to keep in mind
Evidence in moderate-to-advanced CKD is limited; bone outcomes were inconsistently reported, and much of the evidence came from studies primarily designed for type 2 diabetes.