Heart Failure Hospitalization with DPP-4 Inhibitors: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

First, the observational studies comparing DPP-4Is to other active comparators have yielded an inconsistent result on both HF and hHF outcomes [ Table 2 ].[ 16 17 18 19 20 21 22 23 24 25 26 27 ] Second, a meta-analysis of three CVOTs revealed a 12% increased risk of hHF with gliptins with borderline significance (HR 1.12; 95% CI, 1.00–1.25; P = 0.05).[ 28 ] However, other meta-analysis that was done with RCTs of gliptins including three CVOTs showed conflicting results on HF/hHF finding [ Table 3 ].[ 29 30 31 ] So were the findings from the meta-analysis conducted with RCTs of gliptins that excluded three

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This could be further supported by the fact that by applying the Bradford Hill criteria, this association of hHF and saxagliptin use no longer remains highly significant.[ 35 36 ] Moreover, by applying an alternative measure to the hazard ratio, there seems to be no substantial clinically relevant differences in the risk of hHF between saxagliptin, alogliptin, or sitagliptin versus placebo in SAVOR-TIMI, EXAMINE, and TECOS, respectively.[ 37 ] As with any meta-analysis, our study has strength and limitations.

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