medwireNews: Treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor canagliflozin is associated with a reduced risk for anemia-related outcomes among people with type 2 diabetes and chronic kidney disease (CKD), suggests a post-hoc analysis of the CREDENCE trial.
“Anaemia occurs frequently in people with type 2 diabetes and chronic kidney disease, […] is an independent risk factor for adverse kidney and cardiovascular outcomes and is associated with cognitive impairment and poor quality of life,” say Hiddo Heerspink (University Medical Center Groningen, the Netherlands) and colleagues in The Lancet Diabetes & Endocrinology.
They note that “sustained increases in haematocrit and haemoglobin concentration are consistently reported in clinical trials with SGLT2 inhibitors,” and that the drug class has been shown to enhance erythropoiesis in previous research, but “[t]o date, no studies have assessed the effect of SGLT2 inhibitors on anaemia-related clinical events.”
Among the 2202 CREDENCE participants who were randomly assigned to receive canagliflozin 100 mg/day in addition to renin–angiotensin system blockade and guideline-recommended diabetes therapy, 10.4% experienced the composite outcome of investigator-reported anemia or treatment for anemia during a median follow-up of 2.6 years.
By comparison, 15.6% of the 2199 patients who instead received placebo in addition to background therapy experienced this outcome, translating into a significant 35% reduced risk with the SGLT2 inhibitor.
When the components of the primary outcome were analyzed separately, canagliflozin-treated patients were significantly less likely to experience investigator-reported anemia (6.1 vs 10.2%) or to initiate iron preparation (6.2 vs 9.4%) or erythropoiesis-stimulating treatment (2.5 vs 3.9%) than those in the placebo group. Blood transfusion rates were comparable in the two groups, however (2.5 vs 2.7%).
Heerspink and team say that average hemoglobin, hematocrit, and erythrocyte counts increased after randomization among canagliflozin-treated patients, and remained higher in the canagliflozin versus the placebo arm throughout the study. During the follow-up period, average hemoglobin levels were 7.1 g/L higher in the canagliflozin compared with the placebo group, while average hematocrit was 2.4% higher, and mean erythrocyte counts were 0.25 × 10¹² cells/L higher.
The investigators note that “[p]roportional effects of canagliflozin on haemoglobin were greater than effects on serum albumin suggesting that direct effects on erythropoiesis contributed to the observed increases in haemoglobin concentrations.” Indeed, the proportional effect of canagliflozin on hemoglobin, measured by the percentage change in least-squares mean, was 5.40%, compared with just 2.60% for serum albumin levels.
“These findings suggest that a drug originally developed as a glucose lowering agent might have additional value as an adjunct therapy for anaemia in patients with chronic kidney disease,” say Heerspink and team. They caution, however, that the results “require confirmation in a prospective clinical trial.”
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