Table 1.

Cardiovascular events and mortality rates with DPP-4 inhibitors in meta-analyses of phase 2 to 3 randomized controlled trials (excluding the 3 cardiovascular outcome Trials) [48]

DPP-4 inhibitor	Alogliptin	Saxagliptin	Sitagliptin	Linagliptin	Vildagliptin	All DPP-4 inhibitors Monami et al	All DPP-4 inhibitors Xu et al
No. of trials	11	20	25	8	40	70*	35a
Daily dose, mg	12.5–25	2.5–10	100	5–10	1 or 2 × 50	variable	variable
Patients (n) DPP-4 inhibitors vs all comparators	4162 vs 1855	5701 vs 3455	7726 vs 6885	3319 vs 1920	9599 vs 7847	41 959 (total)	29 600 (total)
Primary composite cardiovascular end pointb	0.635 (0–1.406)	0.75 (0.46–1.21)	0.83 (0.53–1.30)c	0.34 (0.16–0.70)	0.84 (0.62–1.14)	0.71 (0.59–0.86); P < 0.001	0.91 (0.53–1.56)
Myocardial infarction	NA	IRR, 0.87	NA	0.52 (0.17–1.54)	0.87 (0.56–1.38)	0.64 (0.44–0.94); P = 0.023	0.71 (0.49–1.03)
Stroke	NA	IRR, 0.75	NA	0.11 (0.02–0.51)	0.84 (0.47–1.50)	0.77 (0.48–1.24); P = 0.290	0.61 (0.37–0.98)
Hospitalization for heart failure	NA	IRR, 0.55	NA	NA	1.08 (0.68–1.70)	NA	1.01 (0.53–1.94)
Cardiovascular mortality	NA	IRR, 0.61	NA	0.74 (0.10–5.33)	0.77 (0.45–1.31)	0.67 (0.39–1.14); P = 0.140	0.91 (0.53–1.56)
All-cause mortality	NA	NA	NA	1.02 (0.23–4.63)	0.91 (0.77–1.08)d	0.60 (0.41–0.88); P = 0.008	0.77 (0.56–1.07)

Comparators are placebo or active glucose-lowering agents. Results are expressed as hazard ratio or odds ratio (95% confidence intervals) and P value when available

DPP-4 dipeptidyl peptidase-4, HR hazard ratio, IRR incidence rate ratio, NA not available

*Placebo (45 trials)/active (18 trials)/both comparators (7 trials)

^aEleven trials vs placebo and 24 trials vs active comparators: no difference between the 2 sets of trials except for stroke: 0.74 (0.25–2.20) vs placebo and 0.58 (0.34–0.99) vs active comparators

^bCardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke

^cSitagliptin (n = 5236) vs placebo (n = 4548) only: HR = 1.01 (0.53–1.86)

^dAll-cause mortality combined with any cardiovascular event