DPP-4 inhibitors moderate the risk of genitourinary tract infections associated with SGLT2 inhibitors

Genito-urinary tract infections (GUTI) are the most common adverse event (AE) during therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i). We evaluated whether dipeptidyl peptidase 4 inhibitors (DPP4i) moderate the risk of GUTI during therapy with SGLT2i, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTI in patients receiving a DPP4i/SGLT2i combination therapy versus those receiving a SGLT2i only. In the 5 trials we retrieved, the pooled RR for genital tract infections (GTI) in patients on a DPP4i/SGLT2i combination therapy versus those on SGLT2i alone was 0.51 (95% C.I. 0.28-0.92). Second, we found that within the Food and Drug Administration AE Reporting System (FAERS), the frequency of GUTI among reports listing both SGLT2i and DPP4i as suspect or concomitant drugs was significantly lower than among reports listing SGLT2i without DPP4i, with a proportional reporting ratio (PRR) of 0.74 (95% C.I. 0.61-0.90). In conclusion, in RCTs and in a large pharmacovigilance database, the combination with a DPP4i appears to reduce the frequency of G(U)TI associated with SGLT2i.