The effects of sodium glucose co-transporter (SGLT) 2 inhibitors on hematocrit levels: a systematic review and meta-analysis of randomized controlled trials.

Background: Previous studies have suggested benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors including improving glycemic control, lower body weight, uric acid-lowering effect and decreasing blood pressure. The aim of this study was to evaluate the effects of SGLT2 inhibitors on hematocrit (Hct) levels in patients with type 2 diabetes mellitus.

Methods: Embase, CENTRAL, PubMed and other databases were searched from the establishment of the database through to July 2020. Randomized controlled trials (RCTs) involving patients with type 2 diabetes mellitus who were treated with SGLT2 inhibitors were analyzed using the random effects model. Stata 12.0 statistical software was used to estimate the weighted mean difference (WMD) and the 95% confidence intervals (CIs).

Results: A total of 40 RCTs were included, comprising 21,050 patients. SGLT2 inhibitors resulted in a significant increase in Hct levels compared to patients treated with a placebo (WMD 2.67%, 95% CI, 2.53 to 2.82; P<0.001). Treatment with 2.5, 5, and 10 mg of dapagliflozin significantly increased Hct levels (WMD 1.96%, 2.27%, and 2.47%, respectively; P<0.001). Administration of 100 and 300 mg of canagliflozin also resulted in a significant increase in Hct (WMD 2.91% and 2.94%, respectively; P<0.001). Similarly, empagliflozin, at concentrations of 10 and 25 mg, caused a significant increase in Hct (WMD 3.39% and 3.44%, respectively; P<0.001). However, treatment with ipragliflozin (12.5 and 50 mg) and ertugliflozin (5 and 15 mg) only resulted in a slight increase in patient Hct levels (WMD 1.26% and 1.98%, respectively for ipragliflozin, P>0.05; WMD 2.24% and 2.64%, respectively for ertugliflozin; P>0.05).

Discussion: SGLT2 inhibitors, as a class of drugs, increased Hct levels in patients with type 2 diabetes, and this increase was slightly more pronounced at higher doses compared to lower doses.

Trial Registration: The protocol of this study has been submitted to the PROSPERO platform (https://www.crd.york.ac.uk/PROSPERO/), and the registration number is CRD42020200699.