Comparative effects of SGLT2 inhibitors on Erythropoiesis: A systematic review and network meta-analysis

Sodium glucose cotransporter-2 inhibitors (SGLT2is) may influence erythropoiesis, but intra-class differences and evidence certainty remain unclear. We evaluated the comparative effects of individual drugs on hematological parameters.

We searched electronic databases for randomized controlled trials comparing any SGLT2i with placebo, standard of care, or another SGLT2i. Outcomes included hemoglobin, hematocrit, red blood cell (RBC) count, erythropoietin, and anemia risk. Pooled estimates were calculated using standardized mean difference (SMD) or odds ratio (OR) with 95% confidence intervals (CI). Certainty of evidence was assessed.

One hundred thirty-six studies (102,882 participants) were included. As a class, SGLT2is significantly increased post-intervention hemoglobin (SMD 0.42 [95% CI 0.33, 0.51]), change-from-baseline hemoglobin (SMD 0.87 [0.65, 1.10]), post-intervention hematocrit (SMD 0.53 [0.44, 0.62]), change-from-baseline hematocrit (SMD 0.91 [0.72, 1.10]), post-intervention RBC count (SMD 0.56 [0.37, 0.75]), change-from-baseline RBC count (SMD 0.94 [0.48, 1.39]), and post-intervention erythropoietin (SMD 0.26 [0.01, 0.52]), but did not reduce anemia risk (OR 0.93 [0.76, 1.14]). Among individual drugs, ertugliflozin showed the largest post-intervention hemoglobin increase, and canagliflozin showed the largest change-from-baseline hemoglobin increase. Evidence certainty was low to very low.

SGLT2is consistently increase hemoglobin, hematocrit, RBC count, and erythropoietin, with intra-class differences observed for specific outcomes. However, low to very low certainty evidence precludes definitive comparative recommendations.