Introduction:  Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) reduce heart failure hospitalizations and cardiovascular death in patients with heart failure (HF). They increase glucose, water and sodium excretion through the kidneys. As HF patients present frequently with low BP and impaired kidney function, physicians are often reluctant to administrate these drugs in HF patients. We explored the risk of hypotension, volume depletion and acute kidney injury (AKI) of SGLT2-i in the available HF studies. 

Methods: We conducted a meta-analysis by pooling available data on reported symptomatic hypotension, volume depletion and AKI from randomized, placebo-controlled trials with SGLT2-i in HF. Furthermore, we explored the correlation between baseline systolic BP and change of the systolic blood pressure (ΔSBP) (defined as a change of the SBP pre- and post-treatment with SGLT2-i) from randomized, placebo-controlled trials with SGLT2-I with HF, diabetes and high cardiovascular risk for or with present cardiovascular disease (CVD). Potential bias was studied with Funnel plots. PUB MED and Cochrane library database were systematically searched for eligible studies.

Results: Trials fulfilling predefined quality criteria and entered the final meta-analysis (Figure 1) including 10,050 patients. Hypotension was reported in 4.52% (219/4,836) on SGLT2-i and in 4.16% (202/4,846) on placebo (RR: 1.09, CI 95% 0.91 – 1.31, p=0.36). Data from eight trials showed a significant negative correlation (r = - 0.75, p=0.02) between baseline SBP and ΔSBP (Figure 2) meaning that patients with low BP had smaller BP declines. Volume depletion occurred in 9.42% (473/5,019) on SGLT2-i and in 8.7% (438/5.031) on placebo (RR: 1.08, CI 95% 0.96 – 1.22, p=0.20). AKI was reported in fewer patients (1.94% (95/4,888)) on SGLT2-i than on placebo (2.85% (140/4,899) providing even less incident cases of AKI (RR: 0.68, CI 95% 0.53 – 0.88, p=0.003). There were not signs of publication bias for any of the explored outcomes

Conclusion:It is concluded that SGLT2-i are not associated with higher risk of hypotension and volume depletion, and SGLT2-i even reduce the risk of AKI. These hypothetical physicians` concerns should not be barriers in the use of SGLT2-i in HF. The prevention of AKI with the long and intermediate term effect of preserving kidney function even supports the consequent use of SGLT2-i in HF.