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Thus, the enzyme cannot be inhibited by more than 100% and the actions of the incretin hormones are glucose-dependent ( Despite the theoretical potential for multiple endogenous DPP-4 substrates to be affected and for the DPP-4 protein to have diverse actions, as discussed in the sections above, pooled safety analyses (119123), and large cardiovascular (CV) safety outcome trials (124127) with the individual drugs, which between them have included many thousands of patients (Table 2), have uniformly shown that DPP-4 inhibitors are well-tolerated and not generally associated with adverse effects