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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