Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease. Issue 6 (June 2022)

• Record Type: Journal Article
• Authors: Cowan, Andrea; Jeyakumar, Nivethika; Kang, Yuguang; Dixon, Stephanie N.; Garg, Amit X.; Naylor, Kyla; Weir, Matthew A.; Clemens, Kristin K.
• Is Part Of: Clinical journal of the American Society of Nephrology. Volume 17:Issue 6(2022)
• Page Start: 835
• Page End: 842
• Publication Date: 2022-06
• Subjects: diabetes mellitus -- renal osteodystrophy -- epidemiology and outcomes -- sodium-glucose transporter 2 inhibitors -- chronic kidney disease
• DOI: 10.2215/CJN.16171221
• Languages: English
• ISSNs: 1555-9041

Abstract

Visual Abstract: Abstract : Background and objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been associated with a higher risk of skeletal fractures in some randomized, placebo-controlled trials. Secondary hyperparathyroidism and increased bone turnover (also common in CKD) may contribute to the observed fracture risk. We aimed to determine if SGLT2 inhibitor use associates with a higher risk of fractures compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, which have no known association with fracture risk. We hypothesized that this risk, if present, would be greatest in patients with lower eGFR. Design, setting, participants, & measurements: We conducted a population-based cohort study in Ontario, Canada between 2015 and 2019 using linked provincial administrative data to compare the incidence of fracture between new users of SGLT2 inhibitors and DPP-4 inhibitors. We used inverse probability of treatment weighting on the basis of propensity scores to balance the two groups of older adults (≥66 years of age) on indicators of baseline health. We compared the 180- and 365-day cumulative incidence rates of fracture between groups. Prespecified subgroup analyses were conducted by eGFR category (≥90, 60 to <90, 45 to <60, and 30 to <45 ml/min per 1.73 m 2 ). Weighted hazard ratios were obtained using Cox proportional hazard regression. Results: After weighting, we identified a total of 38, 994 new users of a SGLT2 inhibitor and 37, 449 new users of a DPP-4 inhibitor and observed a total of 342 fractures at 180 days and 689 fractures at 365 days. The weighted 180- and 365-day risks of a fragility fracture did not significantly differ between new users of a SGLT2 inhibitor versus a DPP-4 inhibitor: weighted hazard ratio, 0.95 (95% confidence interval, 0.79 to 1.13) and weighted hazard ratio, 0.88 (95% confidence interval, 0.88 to 1.00), respectively. There was no observed interaction between fracture risk and eGFR category ( P =0.53). Conclusions: In this cohort study of older adults, starting a SGLT2 inhibitor versus DPP-4 inhibitor was not associated with a higher risk of skeletal fracture, regardless of eGFR.