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Table 1 Summary of the effects of DPP-4 inhibitors and SU agents on CV outcomes

From: Review of the cardiovascular safety of dipeptidyl peptidase-4 inhibitors and the clinical relevance of the CAROLINA trial

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)
  1. aUpper boundary of one-sided repeated CI
  2. bP < 0.001 for non-inferiority
  3. cTrial completed; publication of final data awaited
  4. dThere are no dedicated CVOTs for SUs; data are taken from meta-analyses of randomized clinical trials and observational studies involving SUs
  5. 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
  6. fP = 0.52
  7. gP = 0.047
  8. ↑ = 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