Table 1.
Summary of the effects of DPP-4 inhibitors and SU agents on CV outcomes
| Clinical trial | Intervention | Primary outcome | CV risk | HR, OR or RR (95% CI) |
|---|---|---|---|---|
| DPP-4 inhibitors | ||||
| EXAMINE [8] N = 5380 |
Alogliptin versus placebo | 3-point MACE | ↔ | HR 0.96 (≤ 1.16)a |
| SAVOR-TIMI 53 [7] N = 16,492 |
Saxagliptin versus placebo | 3-point MACE | ↔ | HR 1.00 (0.89–1.12) |
| TECOS [5] N = 14,671 |
Sitagliptin versus placebo | 4-point MACE | ↔ | HR 0.98 (0.88–1.09) |
| CARMELINA [6] N = 6979 |
Linagliptin versus placebo | 3-point MACE | ↔ | HR 1.02 (0.89–1.17)b |
| CAROLINA N = 6041 |
Linagliptin versus glimepiride | 3-point MACE | c [lc] | c [lc] |
| SUs d | ||||
| Rados et al., 2016 [92] MA, 47 RCTs ≥52 wk |
SUs (2nd/3rd generation only) versus other comparators | All-cause mortality | ↔ | P-OR 1.12 (0.96–1.30) |
| CV mortality | ↔ | P-OR 1.12 (0.87–1.42) | ||
| Monami et al., 2013 [93] MA, 115 RCTs (62 reported MACE), ≥24 wk |
All SUs versus other comparators | MACEe | ↔ | MH-OR 1.08 (0.86–1.36)f |
| Mortality | ↑ | MH-OR 1.22 (1.01–1.49)g | ||
| Phung et al., 2013 [94] MA, 12 RCTs, 21 Observational, 6 mo to 10 yr |
All SUs versus other comparators | 4-point MACE | ↑ | RR 1.10 (1.04–1.16) |
| RCTs only | ↔ | RR 0.98 (0.73–1.32) | ||
| Observational only | ↑ | RR 1.11 (1.05–1.18) | ||
| CV mortality | ↑ | RR 1.27 (1.18–1.34) | ||
| RCTs only | ↔ | RR 1.22 (0.63–2.39) | ||
| Observational only | ↑ | RR 1.26 (1.18–1.34) | ||
aUpper boundary of one-sided repeated CI
bP < 0.001 for non-inferiority
cTrial completed; publication of final data awaited
dThere are no dedicated CVOTs for SUs; data are taken from meta-analyses of randomized clinical trials and observational studies involving SUs
eDefined by Monami et al. as CV death, non-fatal myocardial infarction, stroke, acute coronary syndromes, and/or heart failure reported as serious adverse events
fP = 0.52
gP = 0.047
↑ = increase in CV risk; ↔ = neutral effect on CV risk; CV cardiovascular, CVOT cardiovascular outcomes trial, HR Hazard ratio, MA meta-analysis, MACE major adverse cardiovascular event (3-point: CV death, non-fatal MI, or non-fatal stroke; 4-point: 3-point MACE plus hospitalization for unstable angina), MH-OR Mantel-Haenzel odds ratio, P-OR Peto odds ratio, RCT randomized clinical trial, RR relative risk, SU sulfonylurea