Safety outcomes of SGLT2i in the heart failure trials: A systematic review and Meta-analysis

Younes, Ahmed; Salem, Mohammad; Maraey, Ahmed; Nomigolzar, Soroush; Sewell, Kerry; Khalil, Mahmoud; Elzanaty, Ahmed; Saeyeldin, Ayman; Dar, M. Saeed

doi:10.1016/j.ijcard.2022.06.059

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…SGLT2 inhibitors were associated with a significant decrease in severe adverse events. This is consistent with the results of the two included trials and the previous meta-analysis [ 17 , 18 , 26 ]. Severe adverse events remained significantly lower after running the sensitivity analysis.…”

Section: Discussionsupporting

confidence: 92%

“…It can provide more data support for this meta-analysis. Compared with the meta-analysis published by Younes et al, which only focused on the safety outcomes [ 26 ], our present meta-analysis increased the analysis of clinical primary effective endpoints, which is of great significance and provides evidence for clinicians to make decisions in real-world practice.…”

Section: Discussionmentioning

confidence: 93%

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Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

Wang

Gao

Meng³

et al. 2022

Eur J Med Res

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Objectives Heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. Methods Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095. Results Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72–0.85); I2 = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67–0.82); I2 = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67–0.87); I2 = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53–0.93); I2 = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83–0.96); I2 = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death. Conclusions This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or HFmrEF.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 93%

Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

Wang

Gao

Meng³

et al. 2022

Eur J Med Res

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“…Controversial risk of serious adverse events (SAEs) such as genital infections, urinary tract infections (UTIs), and hypotension associated with SGLT2i has limited its clinical use. Younes [ 31 ] found a significantly higher risk of genital infections, urinary tract infections, and hypotension with SGLT2i compared to a placebo. This study preliminary confirmed that SGLT2i was well tolerated and did not increase the risk of hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety evaluation of SGLT2i on blood pressure control in patients with type 2 diabetes and hypertension: a new meta-analysis

Zhang

Zhou

Liu

2023

Diabetol Metab Syndr

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Background The clinical efficacy and safety of SGLT2i in treating patients with type 2 diabetes mellitus and hypertension lack immense data support. Objective To systematically evaluate the clinical efficacy and safety of SGLT2i in patients with type 2 diabetes mellitus and hypertension by collecting the previously published randomized controlled trials on SGLT2i to provide data support for SGLT2i as an adjuvant in the first-line antihypertensive regimen in patients with type 2 diabetes mellitus and hypertension. Methods Randomized controlled trials comparing SGLT2i with a placebo in treating type 2 diabetes with hypertension were screened strictly according to inclusion and exclusion criteria. The primary efficacy endpoints included 24H systolic blood pressure, 24H diastolic blood pressure, office systolic blood pressure, and office diastolic blood pressure. The secondary efficacy endpoints included HbA1c. The safety indicators were hypoglycemia, urinary tract infection, genital infection, and renal impairment.MD was the combined effect size for continuous variables, and RR was the combined effect size for dichotomous variables. Results 10 RCTs with 9913 participants (6293 in the SGLT2i group and 3620 in the control group) were included for analysis.SGLT2i is effective in reducing blood pressure compared with placebo in patients with type 2 diabetes and hypertension, 24HSBP (− 5.06 mmHg, 95% CI [− 7.10, − 3.01], t = − 6.19, P < 0.05), 24HDBP (− 2.39 mmHg, 95% CI [− 4.11, − 0.67], t = − 4.15, P = 0.004), Office SBP (− 4.53 mmHg, 95% CI [− 5.66, − 3.40], t = − 9.50, P < 0.05), Office DBP (− 2.12 mmHg, 95% CI [− 3.42, − 0.82], t = − 4.88, P = 0.001). HbA1c decreased significantly (− 0.57%, 95% CI [− 0.60, − 0.54], z = 37.02, p < 0.01). SGLT2i did not increase hypoglycemia compared to placebo (RR = 1.22, 95% CI [0.916, 1.621], z = 1.36 p = 0.174), urinary tract infection (RR = 1.56, 95% CI [0.96, 2.52], z = 1.79 p = 0.073), risk of renal injury (RR = 0.78, 95% CI [0.54, 1.13], Z = 1.31, P = 0.19), but the risk of genital tract infection increased by 2.32 times (RR = 2.32, 95% CI [1.57, 3.42], Z = 4.23, P = 0.00). Conclusion SGLT2i can effectively control blood pressure and blood glucose and generally has high safety. For patients with type 2 diabetes mellitus and hypertension with a low risk of genital infection, SGLT2i should be considered as an adjuvant drug for a first-line antihypertensive regimen.

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“…The incidence of the main adverse effects of concern with the other foundational treatments of HF [29,31], such as hypotension, significantly worsening renal function and volume depletion, was similar in patients treated with SGLT2i and placebo in several trials. The main adverse event related to SGLT2i is genital tract infection [32,33], which is very uncommon in patients without diabetes [3,4]. In addition, in patients with diabetes, an increased risk for ketoacidosis has been reported; however, the additional absolute risk of this complication is as low as 0.3% per year [34].…”

Section: Safety Profile Of Sglt2i and Consequences On Therapy Initiat...mentioning

confidence: 99%

“…This pragmatic approach makes the vast majority of patients with T2D eligible for SGLT2i treatment. However, in the setting of HF trials, the absolute risk of ketoacidosis remains less than 2% [33].…”

Section: Patients With Hf Eligible For Sglt2i Therapymentioning

confidence: 99%

SGLT2 inhibition in heart failure with reduced or preserved ejection fraction: Finding the right patients to treat

Girerd

Zannad

2023

J Intern Med

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Safety outcomes of SGLT2i in the heart failure trials: A systematic review and Meta-analysis

Cited by 15 publications

References 22 publications

Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

Efficacy and safety evaluation of SGLT2i on blood pressure control in patients with type 2 diabetes and hypertension: a new meta-analysis

SGLT2 inhibition in heart failure with reduced or preserved ejection fraction: Finding the right patients to treat

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