Systematic Reviews
Copyright ©The Author(s) 2024.
World J Diabetes. Oct 15, 2024; 15(10): 2135-2146
Published online Oct 15, 2024. doi: 10.4239/wjd.v15.i10.2135
Table 1 Study-level characteristics of included major cardiovascular outcome trials and associated post-hoc analyses
Year
CVOT
Intervention
Median follow-up (year)
History of MI (yes, %)
History of HF (yes, %)
Post-baseline GLP-1RA/SGLT-2I (yes, %), intervention/placebo
2013EXAMINE[25]Alogliptin1.5N/AN/AN/A
2013SAVOR-TIMI 53[26]Saxagliptin2.1N/AN/AN/A
2015TECOS[27]Sitagliptin3.0N/AN/AN/A
2019
2015
CARMELINA[28]
ELIXA[29]
Linagliptin
Lixisenatide
2.2
2.1
N/A
22
N/A
22
N/A
N/A
2016SUSTAIN-6[30]Semaglutide2.13217[31]1.5/1.2
2016LEADER[32]Liraglutide3.83118[33]2.1/2.81
2017EXSCEL[34]Exenatide3.232[35]164.4/5.8
2018HARMONY OUTCOMES[36]Albiglutide1.547209.7/10.8
2019REWIND[37]Dulaglutide5.416[38]95.2/7.3
2019PIONEER-6[39]Semaglutide1.336[31]12[31]13.5/15.8
2021AMPLITUDE-O[40]Efpeglenatide1.8N/A1817.5/21.2
2015EMPA-REG OUTCOME[41]Empagliflozin3.14710N/A
2017CANVAS[42]Canagliflozin2.429[43]146.2/7.72
2019DECLARE-TIMI 58[44]Dapagliflozin4.221[45]109.5/11.5[19]
2019CREDENCE[46]Canagliflozin2.610[47]156.5/6.9
2020VERTIS CV[48]Ertugliflozin3.548244.9/5.6
Table 2 Effect modification of co-treatment with sodium-glucose co-transporter-2 inhibitors on cardiovascular benefit of glucagon-like peptide-1 receptor agonists and vice versa in type 2 diabetes
Cardiovascular outcome
CovariateInterventionHR with 95%CI
MACENAGLP-1RA vs Placebo0.84 (0.77-0.90)
MACE0GLP-1RA vs Placebo0.89 (0.77-0.99)
MACENASGLT-2I vs Placebo0.90 (0.82-0.98)
MACE0SGLT-2I vs Placebo0.95 (0.82-1.08)
MACE1Combination vs GLP-1RA0.51 (0.16-1.65)
MACE1Combination vs SGLT-2I0.48 (0.15-1.54)
Cardiovascular deathNAGLP-1RA vs Placebo0.85 (0.76-0.94)
Cardiovascular death0GLP-1RA vs Placebo0.88 (0.73-1.07)
Cardiovascular deathNASGLT-2I vs Placebo0.90 (0.79-1.02)
Cardiovascular death0SGLT-2I vs Placebo0.93 (0.76-1.16)
Cardiovascular death1Combination vs GLP-1RA0.58 (0.08-3.39)
Cardiovascular death1Combination vs SGLT-2I0.55 (0.07-3.25)
Fatal and non-fatal MINAGLP-1RA vs Placebo0.89 (0.79-0.98)
Fatal and non-fatal MI0GLP-1RA vs Placebo0.94 (0.79-1.09)
Fatal and non-fatal MINASGLT-2I vs Placebo0.92 (0.81-1.05)
Fatal and non-fatal MI0SGLT-2I vs Placebo0.98 (0.81-1.19)
Fatal and non-fatal MI1Combination vs GLP-1RA0.45 (0.10-2.18)
Fatal and non-fatal MI1Combination vs SGLT-2I0.44 (0.09-2.10)
Fatal and non-fatal strokeNAGLP-1RA vs Placebo0.81 (0.72-0.91)
Fatal and non-fatal stroke0GLP-1RA vs Placebo0.82 (0.67-1.00)
Fatal and non-fatal strokeNASGLT-2I vs Placebo0.94 (0.82-1.08)
Fatal and non-fatal stroke0SGLT-2I vs Placebo0.95 (0.75-1.20)
Fatal and non-fatal stroke1Combination vs GLP-1RA0.86 (0.12-6.23)
Fatal and non-fatal stroke1Combination vs SGLT-2I0.74 (0.10-5.47)
Hospitalization for HFNAGLP-1RA vs Placebo0.90 (0.79-1.02)
Hospitalization for HF0GLP-1RA vs Placebo0.97 (0.80-1.19)
Hospitalization for HFNASGLT-2I vs Placebo0.68 (0.59-0.79)
Hospitalization for HF0SGLT-2I vs Placebo0.75 (0.59-0.96)
Hospitalization for HF1Combination vs GLP-1RA0.26 (0.03-1.88)
Hospitalization for HF1Combination vs SGLT-2I0.33 (0.04-2.53)
Table 3 Effect modification of prior cardiovascular diseases on cardiovascular outcomes of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors in type 2 diabetes
Cardiovascular outcome
Covariate
Intervention
HR with 95%CI
Fatal and non-fatal MIPrior history of MINAGLP-1RA vs Placebo0.91 (0.84-1.01)
Fatal and non-fatal MIPrior history of MI0GLP-1RA vs Placebo1.13 (0.85-1.51)
Fatal and non-fatal MIPrior history of MI1GLP-1RA vs Placebo0.57 (0.30-1.05)
Fatal and non-fatal MIPrior history of MINASGLT-2I vs Placebo0.91 (0.82-1.02)
Fatal and non-fatal MIPrior history of MI0SGLT-2I vs Placebo0.84 (0.66-1.07)
Fatal and non-fatal MIPrior history of MI1SGLT-2I vs Placebo1.09 (0.66-1.80)
Cardiovascular deathPrior history of MINAGLP-1RA vs Placebo0.88 (0.76-0.99)
Cardiovascular deathPrior history of MI0GLP-1RA vs Placebo0.93 (0.59-1.48)
Cardiovascular deathPrior history of MI1GLP-1RA vs Placebo0.74 (0.26-2.01)
Cardiovascular deathPrior history of MINASGLT-2I vs Placebo0.84 (0.72-0.96)
Cardiovascular deathPrior history of MI0SGLT-2I vs Placebo0.92 (0.62-1.32)
Cardiovascular deathPrior history of MI1SGLT-2I vs Placebo0.68 (0.32-1.48)
Hospitalization for HFPrior history of HFNAGLP-1RA vs Placebo0.91 (0.82-1.02)
Hospitalization for HFPrior history of HF0GLP-1RA vs Placebo0.93 (0.61-1.42)
Hospitalization for HFPrior history of HF1GLP-1RA vs Placebo0.84 (0.20-3.67)
Hospitalization for HFPrior history of HFNASGLT-2I vs Placebo0.68 (0.60-0.76)
Hospitalization for HFPrior history of HF0SGLT-2I vs Placebo0.69 (0.52-0.90)
Hospitalization for HFPrior history of HF1SGLT-2I vs Placebo0.62 (0.14-2.80)
Cardiovascular deathPrior history of HFNAGLP-1RA vs Placebo0.86 (0.76-0.97)
Cardiovascular deathPrior history of HF0GLP-1RA vs Placebo0.77 (0.51-1.08)
Cardiovascular deathPrior history of HF1GLP-1RA vs Placebo1.52 (0.30-10.07)
Cardiovascular deathPrior history of HFNASGLT-2I vs Placebo0.84 (0.73-0.96)
Cardiovascular deathPrior history of HF0SGLT-2I vs Placebo0.76 (0.52-1.04)
Cardiovascular deathPrior history of HF1SGLT-2I vs Placebo1.51 (0.29-10.38)