3 Key Takeaways
Plain English Summary- 01Core Finding
Secondary outcomes were changes in red blood cell concentration, erythropoietin (EPO), and iron measures (serum iron, ferritin, transferrin saturation, and hepcidin).
- 02Study Evidence
Tested in a meta-analysis + randomized controlled trial (543 participants) at the meta-analysis stage.
- 03Practical Meaning
Pooled evidence synthesis depends on the quality, heterogeneity, and potential publication bias of included studies.
What This Means for You
In a meta-analysis of randomized clinical trials, compared with control, SGLT2 inhibitor use was associated with small statistically significant increases in hemoglobin and hematocrit levels. The clinical significance of these findings is unclear.
The Discovery
To evaluate the associations between SGLT2 inhibitor use and levels of hemoglobin, hematocrit, and markers of iron metabolism and erythropoiesis compared with placebo (inactive comparison treatment) or active comparator. Primary outcomes were changes in hemoglobin and hematocrit. Secondary outcomes were changes in red blood cell concentration, erythropoietin (EPO), and iron measures (serum iron, ferritin, transferrin saturation, and hepcidin). A total of 85 randomized clinical trials were analyzed (median [IQR] duration, 24 [12-32] weeks), including 70 543 participants (mean [SD] age, 62.4 [9.4] years; 25 334 female [35.9%]). Mean (SD) baseline hemoglobin was 13.6 (1.5) g/dL; baseline hematocrit was 41.5% (4.9). Seventy-eight clinical trials (67 208 participants) compared SGLT2 inhibitors with placebo, and 7 clinical trials (3335 participants) used active comparators, most commonly sitagliptin (2 trials [1158 participants]). From baseline to follow-up, hemoglobin changed by 0.55 g/dL (95% CI, 0.49 to 0.61 g/dL; P <.001) in the SGLT2 inhibitor group, and -0.08 g/dL (95% CI, -0.13 to -0.03 g/dL; P =.003) in the control group (difference, 0.60 g/dL; 95% CI, 0.55 to 0.66 g/dL; P <.001). From baseline to follow-up, hematocrit changed substantially (95% CI, a clinically meaningful level to a clinically meaningful level; P <.001) in the SGLT2 inhibitor group and -0.13% (95% CI, -0.28% to 0.01%; P =.07) in the control group (difference, a clinically meaningful level; 95% CI, a clinically meaningful level to 2.52%; P <.001). Of the 6 secondary outcomes, 4 showed significant associations with SGLT2 inhibitors, including increased EPO (2.35 mIU/mL in SGLT2 inhibitor group vs 0.04 mIU/mL in control group; difference, 2.11 mIU/mL [95% CI, 0.5-3.71 mIU/mL]; P =.01) and decreased transferrin saturation (-a clinically meaningful level in SGLT2 inhibitor group vs -0.10% in control group; difference, -0.84% [95% CI, -1.21% to -0.47%]; P <.001).
How It Works, Simply
This nephrology research focuses on glomerular filtration & renal tubular preservation. Researchers evaluated it using a meta-analysis + Randomized controlled trial (543 participants) at the meta-analysis stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Secondary outcomes were changes in red blood cell concentration, erythropoietin (EPO), and iron measures (serum iron, ferritin, transferrin saturation, and hepcidin).
- 02Study Evidence
Tested in a meta-analysis + randomized controlled trial (543 participants) at the meta-analysis stage.
- 03Practical Meaning
Pooled evidence synthesis depends on the quality, heterogeneity, and potential publication bias of included studies.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Meta-analysis + Randomized controlled trial
Meta-analysis + Randomized controlled trial (543 participants) · Meta-Analysis
Biological Pathway & Modality
Glomerular filtration & renal tubular preservation
Intervention: Sodium-Glucose Cotransporter 2 Inhibitor
Experimental Findings & Endpoints
To evaluate the associations between SGLT2 inhibitor use and levels of hemoglobin, hematocrit, and markers of iron metabolism and erythropoiesis compared with placebo or active comparator.
Primary outcomes were changes in hemoglobin and hematocrit. Secondary outcomes were changes in red blood cell concentration, erythropoietin (EPO), and iron measures (serum iron, ferritin, transferrin saturation, and hepcidin).
A total of 85 randomized clinical trials were analyzed (median [IQR] duration, 24 [12-32] weeks), including 70 543 participants (mean [SD] age, 62.4 [9.4] years; 25 334 female [35.9%]). Mean (SD) baseline hemoglobin was 13.6 (1.5) g/dL; baseline hematocrit was 41.5% (4.9).
Seventy-eight clinical trials (67 208 participants) compared SGLT2 inhibitors with placebo, and 7 clinical trials (3335 participants) used active comparators, most commonly sitagliptin (2 trials [1158 participants]). From baseline to follow-up, hemoglobin changed by 0.55 g/dL (95% CI, 0.49 to 0.61 g/dL; P <.001) in the SGLT2 inhibitor group, and -0.08 g/dL (95% CI, -0.13 to -0.03 g/dL; P =.003) in the control group (difference, 0.60 g/dL; 95% CI, 0.55 to 0.66 g/dL; P <.001).
From baseline to follow-up, hematocrit changed substantially (95% CI, a clinically meaningful level to a clinically meaningful level; P <.001) in the SGLT2 inhibitor group and -0.13% (95% CI, -0.28% to 0.01%; P =.07) in the control group (difference, a clinically meaningful level; 95% CI, a clinically meaningful level to 2.52%; P <.001). Of the 6 secondary outcomes, 4 showed significant associations with SGLT2 inhibitors, including increased EPO (2.35 mIU/mL in SGLT2 inhibitor group vs 0.04 mIU/mL in control group; difference, 2.11 mIU/mL [95% CI, 0.5-3.71 mIU/mL]; P =.01) and decreased transferrin saturation (-a clinically meaningful level in SGLT2 inhibitor group vs -0.10% in control group; difference, -0.84% [95% CI, -1.21% to -0.47%]; P <.001).
Clinical Translation & Practice Context
In a meta-analysis of randomized clinical trials, compared with control, SGLT2 inhibitor use was associated with small statistically significant increases in hemoglobin and hematocrit levels.
The clinical significance of these findings is unclear.
The Bottom Line · Clinical Pearl
“In a meta-analysis of randomized clinical trials, compared with control, SGLT2 inhibitor use was associated with small statistically significant increases in hemoglobin and hematocrit levels.”
Published in JAMA · Current Stage: Meta-Analysis