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Meta-Analysis
. 2022 Jan;26(2):540-547.
doi: 10.1111/jcmm.17115. Epub 2021 Dec 8.

Effects of SGLT2 inhibitors on haematocrit and haemoglobin levels and the associated cardiorenal benefits in T2DM patients: A meta-analysis

Qi Tian  1 , Keyu Guo  1 , Jiayi Deng  2 , Yanjun Zhong  2 , Lin Yang  1
Affiliations
Meta-Analysis

Effects of SGLT2 inhibitors on haematocrit and haemoglobin levels and the associated cardiorenal benefits in T2DM patients: A meta-analysis

Qi Tian et al. J Cell Mol Med. 2022 Jan.

Abstract

To explore the effect and magnitude of effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on haematocrit and haemoglobin and the related cardiorenal benefits in patients with type 2 diabetes mellitus (T2DM), PubMed, Web of Science, CENTRAL and EMBASE were searched to identify eligible trials. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Seventy-eight studies were included in the meta-analysis. SGLT2 inhibitors significantly increased haematocrit and haemoglobin levels compared with control (total WMD 2.27% [95% CI 2.08, 2.47] and 6.20 g/L [95% CI 5.68, 6.73], respectively). Except for dapagliflozin (p = 0.000), no notable dose-dependent relationship was revealed for other SGLT2 inhibitors. The effect could be sustained or even slightly increased with long-term therapy (coef. =0.009, 95% CI [0.005, 0.013], p = 0.000). In subgroup analyses, haematocrit elevation increased with higher body mass index (BMI). A greater haematocrit elevation could be observed in white patients or when compared with active controls. In conclusion, SGLT2 inhibitors increased haematocrit and haemoglobin levels in T2DM patients. Changes in haematocrit and haemoglobin seem to be surrogate markers of improvement in renal metabolic stress, and important mediators involved in cardiorenal protection.

Keywords: SGLT2 inhibitors; cardiorenal protection; haematocrit; haemoglobin; meta-analysis; type 2 diabetes mellitus.

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Conflict of interest statement

All authors declared that there were no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram
FIGURE 2
FIGURE 2
Risk‐of‐bias graph
FIGURE 3
FIGURE 3
Meta‐analysis of WMD and 95% CI of changes in haematocrit (%) level for SGLT2 inhibitors, stratified by drug. The WMD of each dose was a combined result of multiple observations. WMDs are from a random‐effects model analysis. CI: confidence interval; WMD: weighted mean difference
FIGURE 4
FIGURE 4
Meta‐analysis of WMD and 95% CI of changes in EPO (IU/L) levels for SGLT2 inhibitors. WMDs are from a random‐effects model analysis. CI: confidence interval; WMD: weighted mean difference
FIGURE 5
FIGURE 5
Subgroup analyses based on comparator type and baseline characteristics revealed that there was a significant difference in the increase in haematocrit levels between the treatment and control groups when stratified by race, type of the comparator, baseline duration of T2DM or BMI. No significant differences were found for age, sex, baseline HbAlc, eGFR or HCT. HbAlc: glycated haemoglobin; eGFR: estimated glomerular filtration rate; BMI: body mass index; HCT: haematocrit
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