Table 4.
Risk ratios (95% CIs) for individual MACE reported in integrated analyses of DPP-4 inhibitors and GLP-1 agonists
| First author [reference] | Drug | CV event category | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| CV death | MI | Stroke | ACS | Arrhythmia | TIA | Heart failure | All death | UAP | ||
| White, 2013 [26] | Alogliptin | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Iqbal, 2014 [24]a | Saxagliptin | 0.61 (>1) | 0.87 (>1) | 0.75 (>1) | NR | NR | NR | 0.55 (>1) | NR | NR |
| Engel, 2013 [23] | Sitagliptin | 0.95 (0.40–2.30) | NR | NR | NR | NR | NR | NR | NR | NR |
| Rosenstock, 2015 [21] | Linagliptin | 1.04 (0.42–2.60) | 0.86 (0.47–1.56) | 0.34 (0.15–0.75) | NR | NR | 0.09 (0.01–0.75) | NR | 0.89 (0.45–1.75) | 1.08 (0.56–2.06)b |
| McInnes, 2015 [25] | Vildagliptin 50 mg od and bd | 0.77 (0.45–1.31) | 0.97 (0.56–1.38) | 0.84 (0.47–1.50) | NR | NR | NR | 1.08 (0.68–1.70) | NR | NR |
| Wang, 2016 [41] | Alogliptin | 0.78 (0.59–1.03) | 1.06 (0.86–1.31) | 0.86 (0.54–1.36) | NR | 1.25 (0.44–3.52) | NR | 1.22 (0.92–1.60) | 0.86 (0.69–1.07) | 0.86 (0.58–1.28) |
| Linagliptin | 1.85 (0.56–6.08) | 0.90 (0.45–1.78) | 0.49 (0.24–1.00) | NR | 1.47 (0.64–3.42) | NR | 1.87 (0.84–4.15) | 0.94 (0.38–2.33) | 1.58 (0.52–4.76) | |
| Saxagliptin | 1.00 (0.84–1.19) | 0.93 (0.79–1.10) | 1.12 (0.90–1.40) | NR | 1.14 (0.47–2.78) | NR | 1.23 (1.03–1.46) | 1.09 (0.95–1.26) | 1.18 (0.88–1.58) | |
| Sitagliptin | 1.03 (0.89–1.19) | 0.98 (0.83–1.15) | 0.91 (0.73–1.13) | NR | 1.14 (0.54–2.41) | NR | 0.98 (0.82–1.18) | 1.00 (0.89–1.13) | 0.86 (0.68–1.10) | |
| Vildagliptin | 2.19 (0.53–9.01) | 0.20 (0.04–1.00) | 0.26 (0.08–0.84) | NR | 0.91 (0.34–2.45) | NR | 0.80 (0.16–4.09) | 0.95 (0.35–2.60) | NR | |
| Udell, 2015 [37] | Alogliptin and saxagliptin | NR | NR | NR | NR | NR | NR | 1.25 (1.08–1.45) | NR | NR |
| Abbas, 2016 [42] | Alogliptin, saxagliptin, and sitagliptin | 1.01 (0.91–1.12) | 0.99 (0.89–1.09) | 1.00 (0.86–1.16) | NR | NR | NR | 1.12 (1.00–1.25) | NR | NR |
| Kundu, 2016 [39] | Alogliptin, saxagliptin, and sitagliptin | NR | NR | NR | NR | NR | NR | 1.14 (0.97–1.34)b | NR | NR |
| Agarwal, 2014 [33] | DPP-4 inhibitors | 0.95 (0.82–1.09) | 0.98 (0.86–1.10) | 0.92 (0.77–1.11) | NR | NR | NR | NR | 1.00 (0.90–1.13) | NR |
| Kongwatcharapong, 2016 [38] | DPP-4 inhibitors | NR | NR | NR | NR | NR | NR | 1.106 (0.995–1.228) | NR | NR |
| Li, 2016 [40] | DPP-4 inhibitors | NR | NR | NR | NR | NR | NR |
0.97 (0.61–1.56) 1.13 (1.00–1.26)b |
NR | NR |
| Monami, 2013 [29] | DPP-4 inhibitors | 0.67 (0.39–1.14) | 0.64 (0.44–0.94)c | 0.77 (0.48–1.24) | NR | NR | NR | NR | 0.60 (0.41–0.88) | NR |
| Monami, 2014 [34] | DPP-4 inhibitors | NR | NR | NR | NR | NR | NR | 1.19 (1.03–1.30)d | NR | NR |
| Patil, 2012 [30] | DPP-4 inhibitors | NR | NR | NR | 0.40 (0.18–0.88)e | NR | NR | NR | NR | NR |
| Savarese, 2015 [36] | DPP-4 inhibitors (STFU) | 1.03 (0.51–2.07) | 0.58 (0.36–0.94)f | 0.66 (0.36–1.21) | NR | NR | NR | 0.67 (0.32–1.40) | 1.064 (0.56–2.00) | NR |
| DPP-4 inhibitors (LTFU) | 0.962 (0.84–1.10) | 0.94 (0.84–1.06) | 0.95 (0.79–1.14) | NR | NR | NR | 1.16 (1.01–1.33)g | 1.01 (0.91–1.13) | NR | |
| Wu, 2013 [31] | DPP-4 inhibitors | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Wu, 2014 [35] | DPP-4 inhibitors | 0.97 (0.85–1.11) | NR | 0.98 (0.81–1.18) | 0.97 (0.87–1.08) | NR | NR | 1.16 (1.01–1.33)h | 1.01 (0.91–1.13) | NR |
| Zhang, 2014 [32] | DPP-4 inhibitors | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Fisher, 2015 [53] | Albiglutide | 1.06 (0.55–2.06) | 0.96 (0.52–1.76) | 1.02 (0.45–2.33) | NR | NR | NR | NR | NR | 0.77 (0.25–2.37)b |
| Ferdinand, 2016 [54] | Dulaglutide | 0.35 (0.07–1.87)i | 0.35 (0.13–0.95)i | 1.61 (0.42–6.20)i | NR | NR | NR | 2.02 (0.41–9.88)b, i | 0.50 (0.18– 1.38)i | 0.28 (0.05–1.46)b, i |
| Ratner, 2011 [51] | Exenatide bd | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Marso, 2011 [50] | Liraglutide | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Seshasai, 2015 [52] | Taspoglutide | NR | NR | NR | NR | NR | NR | NR | 0.89 (0.38–2.07) | NR |
| Wang, 2016 [41] | Albiglutide | NR | 1.20 (0.57–2.51) | 0.57 (0.19–1.69) | NR | 2.01 (0.70–5.73) | NR | 0.45 (0.17–1.17) | 0.56 (0.12–2.59) | 0.87 (0.32–2.38) |
| Dulaglutide | NR | 0.21 (0.04–0.98) | 2.83 (0.60–13.28) | NR | NR | NR | NR | NR | NR | |
| Exenatide | 1.68 (0.28–9.87) | 0.81 (0.29–2.25) | 1.56 (0.45–5.41) | NR | 2.83 (1.06–7.57) | NR | 1.92 (0.39–9.50) | 1.17 (0.47–2.89) | 0.83 (0.22–3.08) | |
| Liraglutide | NR | 1.03 (0.43–2.47) | 1.06 (0.33–3.37) | NR | 0.74 (0.20–2.77) | NR | 5.52 (0.90–33.95) | 0.47 (0.02–8.88) | NR | |
| Lixisenatide | 0.98 (0.78–1.23) | NR | 2.74 (0.38–19.50) | NR | 4.50 (0.24–84.78) | NR | NR | 1.06 (0.87–1.29) | NR | |
| Li, 2016 [56] | GLP-1 receptor agonists | NR | NR | NR | NR | NR | NR | 0.62 (0.31–1.22) | NR | NR |
| Monami, 2013 [12] | GLP-1 receptor agonists | 0.63 (0.24–1.66) | 0.87 (0.48–1.56) | 0.87 (0.37–2.05) | NR | NR | NR | NR | 0.89 (0.46–1.70) | NR |
ACS acute coronary syndrome, bd twice daily, CV cardiovascular, LTFU long-term follow-up (>29 weeks), MI myocardial infarction, od once daily, NR not reported, STFU short-term follow-up (<29 weeks), TIA transient ischemic attack, UAP unstable angina pectoris
a95% Confidence intervals not reported but included one based on visual inspection of graph [24]
bRequiring hospitalization
c P = 0.023 DPP-4 inhibitors versus placebo/active comparators
d P = 0.015 DPP-4 inhibitors versus placebo/active comparators
eTerm included nonfatal MI
f P = 0.028 DPP-4 inhibitors versus placebo/active comparators
g P = 0.034 DPP-4 inhibitors versus placebo/active comparators
h P = 0.04 DPP-4 inhibitors versus placebo/active comparators
iAdjusted 98.02% CI