A 2023 network meta-analysis based on Bayesian methods indirectly compared sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with established heart failure. A total of 5 randomized controlled trials were included that evaluated 4 different treatment strategies among 21,927 patients. No significant differences were found in the composite of cardiovascular death or hospitalization for heart failure between dapagliflozin and empagliflozin (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.66 to 1.55), dapagliflozin and sotagliflozin (OR 1.54, 95% CI 0.91 to 2.65), and empagliflozin and sotagliflozin (OR 1.53, 95% CI 0.90 to 2.69). The comparisons of dapagliflozin and empagliflozin (OR 0.92, 95% CI 0.71 to 1.18), dapagliflozin and sotagliflozin (OR 1.05, 95% CI 0.68 to 1.59), and empagliflozin and sotagliflozin (OR 1.14, 95% CI 0.74 to 1.73) revealed no significant differences in all-cause mortality. Cardiovascular death did not differ significantly when dapagliflozin was compared to empagliflozin (OR 0.94, 95% CI 0.71 to 1.23), dapagliflozin was compared to sotagliflozin (OR 0.96, 95% CI 0.61 to 1.55), and empagliflozin was compared to sotagliflozin (OR 1.03, 95% CI 0.64 to 1.66). There was no significant difference in hospitalization for heart failure between dapagliflozin and empagliflozin (OR 1.13, 95% CI 0.64 to 1.97), dapagliflozin and sotagliflozin (OR 1.56, 95% CI 0.74 to 3.15), and empagliflozin and sotagliflozin (OR 1.39, 95% CI 0.68 to 2.78). [1]
Subgroup analyses in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) also observed no differences between dapagliflozin and empagliflozin for evaluated outcomes. It was determined that there were no significant differences in major efficacy outcomes among SGLT2 inhibitors in patients with established heart failure; however, sotagliflozin was identified to be associated with the lowest risk of cardiovascular death or hospitalization for heart failure, and dapagliflozin was identified to be associated with the lowest risk of all-cause and cardiovascular mortality. [1]
A 2022 network meta-analysis evaluated the relative efficacy of five SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on cardiorenal outcomes. Ten cardiovascular outcome trials were included in the analysis. Compared to placebo, canagliflozin (hazard ratio [HR] 0.64; 95% CI 0.53 to 0.77), dapagliflozin (HR 0.7; 95% CI 0.62 to 0.79), empagliflozin (HR 0.68; 95% CI 0.59 to 0.78), ertugliflozin (HR 0.7; 95% CI 0.54 to 0.9), and sotagliflozin (HR 0.66; 95% CI 0.56 to 0.77) all reduced hospitalization for heart failure. None of the five agents reduced myocardial infarction or stroke. Compared with ertugliflozin, empagliflozin reduced cardiovascular death or hospitalization for heart failure (HR 0.81; 95% CI 0.67 to 0.99); both empagliflozin (HR 0.65; 95% CI 0.45 to 0.93) and dapagliflozin (HR 0.69; 95% CI 0.52 to 0.92) reduced and kidney function progression. Surface under the cumulative ranking cure (SUCRA) probability to rank treatments was calculated. Canagliflozin had the greatest SUCRA value for reduction of major adverse cardiovascular events (MACE), stroke, and hospitalization for heart failure; empagliflozin had the greatest value for reduction of myocardial infarction, cardiovascular death, cardiovascular death or hospitalization for heart failure, kidney function progression, and all-cause death. [2]
A 2021 systematic review and meta-analysis investigated the comparative efficacy of individual SGLT2 inhibitors, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. A total of 64 trials (N= 74,874) were included; the primary endpoint was all-cause mortality, while secondary endpoints included cardiovascular mortality and worsening heart failure. Compared to placebo, empagliflozin and canagliflozin were found to improve all three endpoints (all-cause mortality: empagliflozin risk ratio [RR] 0.67, 95% CI 0.55 to 0.8 and canagliflozin RR 0.85, 95% CI 0.75 to 0.97; cardiovascular mortality: empagliflozin RR 0.61, 95% CI 0.49 to 0.77 and canagliflozin RR 0.85, 95% CI 0.73 to 0.99; and worsening heart failure: empagliflozin 0.66, 95% CI 0.5 to 0.86 and canagliflozin 0.62, 95% CI 0.52 to 0.75), while dapagliflozin improved worsening heart failure (RR 0.75, 95% CI 0.62 to 0.88). Empagliflozin, compared with other SGLT2 inhibitors, was superior for reductions in all-cause (vs. canagliflozin RR 0.78, 95% CI 0.62 to 0.98; vs. dapagliflozin RR 0.72, 95% CI 0.58 to 0.9) and cardiovascular mortality (vs. canagliflozin RR 0.72, 95% CI 0.55 to 0.95; vs. dapagliflozin RR 0.52, 95% CI 0.48 to 0.85). Similar effects were seen between empagliflozin, canagliflozin, and dapagliflozin on improvement of worsening heart failure. Ertugliflozin was found to have no effect on any of the endpoints. [3]
A 2021 network meta-analysis evaluated the relative efficacy of various SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on cardiorenal outcomes. A total of 14 cardiovascular or renal outcome trials were included in the analysis. Sotagliflozin (HR 0.76; 95% CI 0.61 to 0.94) lowered the risk of MACE, as did subcutaneous semaglutide and albiglutide. A lower risk of hospitalization for heart failure was seen for sotagliflozin (HR 0.59; 95% CI 0.4 to 0.90), canagliflozin (HR 0.58; 95% CI 0.38 to 0.87), and empagliflozin (HR 0.59; 95% CI 0.37 to 0.92). Risk of kidney function progression was lowered with dapagliflozin (HR 0.6; 95% CI 0.47 to 0.78) and empagliflozin (HR 0.61; 95% CI 0.43 to 0.87). Cardiovascular death was lowered with empagliflozin (HR 0.63; 95% CI 0.47 to 0.84) and oral semaglutide, while sotagliflozin (HR 0.65; 95% CI 0.47 to 0.91) and albiglutide lowered risk for myocardial infarction. Risk of stroke was lowered with sotagliflozin (HR 0.56; 95% CI 0.37 to 0.85) and subcutaneous semaglutide. Oral semaglutide and empagliflozin (HR 0.65; 95% CI 0.43 to 0.96) were found to lower risk of all-cause death. [4]
A 2020 meta-analysis that evaluated SGLT2 inhibitors and their effects on heart failure hospitalization in patients with type 2 diabetes. A total of 55,763 patients with type 2 diabetes were randomized to either SGLT2 inhibitors (n= 31,172) or placebo (n= 24,591) within the included trials. Subgroup analyses determined that canagliflozin (RR 0.60; 95% CI 0.49 to 0.72; p<0.00001), dapagliflozin (RR 0O.73; 95% CI 0.62 to 0.85; p<0.0001), empagliflozin (RR 0.52; 95% CI 0.28 to 1.00; p= 0.05), and ertugliflozin (RR 0.70; 95% CI, 0.54 to 0.90; p= 0.006) all significantly decreased the occurrence of heart failure hospitalization. However, there was noted to be significant heterogeneity among the eight trials included for analysis (I2= 74%). Subgroup analyses of the various agents and their respective effects on MACE found canagliflozin (RR 0.81; 95% CI 0.68 to 0.95; p<0.01) and empagliflozin (RR 0.86; 95% CI 0.75 to 0.99; p<0.04) to significantly decrease MACE occurrence. No significant heterogeneity was identified for the outcome of MACE (I2= 20%). Compared to placebo, no agent appeared to significantly decrease the occurrence of cardiovascular death. Significant heterogeneity was present in the analysis for cardiovascular death (I2= 88%). Notably, dapagliflozin was the only agent to significantly decrease the occurrence of death from any cause (RR 0.89; 95% CI 0.81 to 0.98; p= 0.02). Overall, it is difficult to distinguish the effects of all SGLT2 inhibitors due to a paucity of relevant trials and significant heterogeneity between trials for relevant outcomes. [5]
A 2023 study conducted a cost-effectiveness analysis in order to compare dapagliflozin and empagliflozin in patients with heart failure with reduced ejection fraction. The model estimated the expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) for both medications. Patients 65 years of age at entry were included and their health outcomes were simulated over a lifetime horizon, based on the US healthcare system. The incremental expected lifetime cost of treating patients with dapagliflozin compared to empagliflozin was $37,684. This resulted in an ICER of $44,763 per QALY. The authors concluded that dapagliflozin may offer a greater lifetime economic value compared with empagliflozin. [6]