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) |
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 | |||||||
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) |