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Table 1 Major characteristics of the outcome trials included in the network meta-analysis

From: Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis

Studies Year ClinicalTrials.gov Identifier Intervention Patients (Antidiabetic drug/placebo) Primary endpoints HRa (95% CI) of MACEb HR (95% CI) of all-cause mortality
GLP-1 RA vs. placebo
 ELIXA [24] 2015 NCT01147250 Lixisenatide vs. placebo 6068 (3034/3034) A composite of the first occurrence of any of the following: death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalisation for unstable angina 1.02 (0.89–1.17) 0.94 (0.78–1.13)
 LEADER [9] 2016 NCT01179048 Liraglutide vs. placebo 9340 (4668/4672) A composite of the first occurrence of death from cardiovascular causes, nonfatal MI (including silent), or nonfatal stroke 0.87 (0.78–0.97) 0.85 (0.74–0.97)
 SUSTAIN-6 [22] 2016 NCT01720446 Semaglutide vs. placebo 3297 (1648/1649) A composite of the first occurrence of death from cardiovascular causes, nonfatal MI (including silent), or nonfatal stroke 0.74 (0.58–0.95) 1.05 (0.74–1.50)
 HARMONY OUTCOMES [12] 2018 NCT02465515 Albiglutide vs. placebo 9463 (4731/4732) A composite of death from cardiovascular causes, MI, and stroke 0.78 (0.68–0.90) 0.95 (0.79–1.16)
 EXSCEL [13, 27] 2018 NCT01144338 Exenatide vs. placebo 10,782 (5394/5388) A composite of death from cardiovascular causes, nonfatal MI, and nonfatal stroke 0.90 (0.82–1.00) 0.88 (0.77–1.00)
DPP-4 inhibitor vs. placebo
 SAVOR-TIMI 53 [26] 2013 NCT01107886 Saxagliptin vs. placebo 16,492 (8280/8212) A composite of cardiovascular death, nonfatal MI, or nonfatal ischaemic stroke 1.00 (0.89–1.12) 1.11 (0.96–1.27)
 EXAMINE [25] 2013 NCT00968708 Alogliptin vs. placebo 5380 (2701/2679) A composite of death from cardiovascular causes, nonfatal MI, or nonfatal stroke 0.96 (≤ 1.16)c 0.98 (0.86–1.12)
 TECOS [23] 2015 NCT00790205 Sitagliptin vs. placebo 14,523 (7257/7266) A composite of the first confirmed event of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalisation for unstable angina 0.99 (0.89–1.10) 1.01 (0.90–1.14)
 CARMELINA [16] 2018 NCT01897532 Linagliptin vs. placebo 6979 (3494/3485) A composite of the first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke 1.02 (0.89–1.17) 0.98 (0.84–1.13)
SGLT-2 inhibitor vs. placebo
 EMPA-REG OUTCOME [10, 28] 2015 NCT01131676 Empagliflozin vs. placebo 7020 (4687/2333) A composite of death from cardiovascular causes, nonfatal MI (excluding silent MI), or nonfatal stroke 0.86 (0.74–0.99) 0.68 (0.57–0.82)
 CANVAS [15] 2017 NCT01032629 Canagliflozin vs. placebo 4330 (2888/1442) A composite of death from cardiovascular causes, nonfatal MI, or nonfatal stroke 0.88 (0.75–1.03) 0.84 (0.70–1.01)
 CANVAS-R [15] 2017 NCT01989754 Canagliflozin vs. placebo 5812 (2907/2905) A composite of death from cardiovascular causes, nonfatal MI, or nonfatal stroke 0.82 (0.66–1.01) 0.92 (0.70–1.21)
 DECLARE-TIMI 58 [14] 2018 NCT01730534 Dapagliflozin vs. placebo 17,160 (8582/8578) A composite of cardiovascular death, MI, or ischaemic stroke 0.93 (0.84–1.03) 0.93 (0.82–1.04)
 CREDENCE [18] 2019 NCT02065791 Canagliflozin vs. placebo 4401 (2202/2199) A composite of cardiovascular death, MI, or stroke 0.80 (0.67–0.95) 0.83 (0.68–1.02)
  1. DPP-4: dipeptidyl peptidase-4; GLP-1: glucagon-like peptide-1; HR: hazard ratio; MACE: major adverse cardiovascular events; MI: myocardial infarction; RA: receptor agonist; SGLT-2: sodium-glucose co-transporter 2; 95% CI: 95% confidence interval
  2. aHR (antidiabetic drug vs. placebo) of the outcomes evaluated in each trial
  3. bMACE was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular mortality
  4. cOnly upper bound of the one-sided 95% CI was reported (α: 0.01)