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Sodium-glucose cotransporter 2 inhibition: which patient with chronic kidney disease should be treated in the future?

ABSTRACT: The advent of sodium-glucose cotransporter 2 (SGLT2) inhibitors represents a major advance for people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). The results of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial have clearly demonstrated that canagliflozin prevents kidney failure and cardiovascular events. The results from three other large-scale randomized trials, collectively enrolling >30?000 participants, have provided further evidence that the effects of SGLT2 inhibition on major kidney outcomes in people with T2DM may be present across the class, although this will only be known for certain when Dapagliflozin and Renal Outcomes and Cardiovascular Mortality in Patients with CKD (DAPA-CKD) (NCT03036150) and The Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY) (NCT03594110) are reported over coming years. Importantly, the benefits of SGLT2 inhibition have been achieved in addition to the current standard of care. This review summarizes evidence for SGLT2 inhibition in people with T2DM and CKD, evaluates key patient characteristics and concomitant drug use that may influence the use of these drugs in people with CKD, discusses current guideline recommendations and explores how these drugs may be used in people with CKD in the future, including in combination with other treatments.

SUBMITTER: Neuen BL

PROVIDER: S-EPMC6993192 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Sodium-glucose cotransporter 2 inhibition: which patient with chronic kidney disease should be treated in the future?

Neuen Brendon L BL Jardine Meg J MJ Perkovic Vlado V

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20200101 Suppl 1

The advent of sodium-glucose cotransporter 2 (SGLT2) inhibitors represents a major advance for people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). The results of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial have clearly demonstrated that canagliflozin prevents kidney failure and cardiovascular events. The results from three other large-scale randomized trials, collectively enrolling >30 000 participants, have pr ...[more]

PMID: 32003833

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Project description:Background and objectivesSodium-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, & measurementsWe 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 m2). Weighted hazard ratios were obtained using Cox proportional hazard regression.ResultsAfter 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).ConclusionsIn 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.

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Sodium-glucose cotransporter 2 inhibition: which patient with chronic kidney disease should be treated in the future?

Publications

Sodium-glucose cotransporter 2 inhibition: which patient with chronic kidney disease should be treated in the future?

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