BACKGROUND & AIMS: Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of 
Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in 
Myocardial Infarction-53) reported a significant increase in the risk of 
hospitalizations for heart failure in patients treated with saxagliptin in 
comparison with placebo. Aim of the present meta-analysis is the systematic 
collection and synthesis of information on treatment-emergent cases of acute 
heart failure described in randomized clinical trials with DPP4.
DATA SOURCES: An extensive Medline, Embase, and Cochrane Database search for 
"vildagliptin", "sitagliptin", "saxagliptin", "alogliptin", "linagliptin", and 
"dutogliptin" was performed, collecting all randomized clinical trials on humans 
up to October 1st, 2013. Studies were included if they satisfied the following 
criteria: i) randomized trials, ii) duration ≥24 weeks; iii) on type 2 diabetes; 
iv) comparison of DPP4i with placebo or active drugs. The principal outcome was 
the effect of DPP4i on the incidence of acute heart failure. A total of 84 
eligible trials was identified. The overall risk of acute heart failure was 
higher in patients treated with DPP4i in comparison with those treated with 
placebo/active comparators (MH-OR: 1.19[1.03; 1.37]; p = 0.015). When trials 
with non-cardiovascular outcomes were analysed separately no signal of risk was 
detectable.
CONCLUSION: Available data from RCTs suggest that DPP4i could be associated with 
an increased risk of heart failure, without any clear evidence of differences 
among drugs of the class. Although it is plausible that the risk is greater in 
some sub-populations of patients, current evidence is not yet sufficient to 
identify susceptible patients.