BACKGROUND: In studying the therapeutic evidence of innovative drug treatments, 
increasing attention is being devoted to differentiating between results that 
indicate no significant differences among the treatments under examination ("no 
proof of difference") and results that demonstrate the therapeutic equivalence 
among the treatments ("proof of no difference").
AIM: Our analysis was aimed at evaluating the degree of therapeutic equivalence 
for dipeptidylpeptidase-4 (DPP-4) inhibitors given in type 2 diabetes as 
monotherapy or in combination with metformin.
METHODS: Equivalence was determined by developing a standard Forest plot that 
incorporated the information on margins previously reported in randomized trials 
on these agents. The end point was HbA1c change from baseline; the equivalence 
margin was set at ±0.25% change in HbA1c. The clinical material was obtained 
from a systematic review on this topic.
RESULTS: Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but 
not saxagliptin) met the equivalence criterion when compared with one another. 
Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and 
vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the 
equivalence criterion.
CONCLUSIONS: Considering the most recent therapeutic guidelines, our results are 
of interest particularly as regards the information on DPP-4 inhibitors in 
combination with metformin. Four of the five DPP-4 inhibitors under examination 
clearly showed to have the same effectiveness; the fifth agent-alogliptin-failed 
to meet the equivalence criterion, but only because its superiority could not be 
excluded.