Lower Risk for SGLT2i-Associated Genitourinary Infection With DPP-4i

Researchers evaluated a meta-analysis of randomized controlled trials and an analysis of the FDA AE Reporting System to determine whether combination DPP4i/SGLT2i medication lowers risk of GUTI.

Use of dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with sodium-glucose cotransporter 2 inhibitors (SGLT2i) may help lower the risk of genitourinary tract infections (GUTI) which are often an adverse effect of the latter medication, according to a meta-analysis published in Diabetes, Obesity & Metabolism.

The researchers retrieved 81 articles and performed a meta-analysis of 5 high-quality randomized controlled trials that reported the frequency of GUTIs in patients who received DPP-4i/SGLT2i combination therapy vs SGLT2i alone. Using a random effect model, they found a 49% lower risk of genital tract infections (GTIs) in patients who received DPP-4i/SGLT2i combination medication compared with patients who received an SGLT2i alone. No reduction in the incidence of urinary tract infections (UTIs) was reported; however, SGLT2i use is often associated with an increased risk for GTIs and not UTIs.

The investigators then analyzed data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2014 to 2016 and found a 26% lower frequency of GUTIs in patients who received DPP-4i/SGLT2i combination medication vs an SGLT2i alone. Although FAERS does not distinguish between GTIs and UTIs, and more that 90% of GUTIs are reported as UTIs, these data strongly confirm the findings of the researchers’ meta-analysis.

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While alternative theories may suggest other reasons for this moderation in GTIs, combination treatment with a DPP-4i appears to reduce the frequency of GUTIs associated with SGLT2is. The investigators noted that “DPP-4i/SGLT2i associations are being developed as single-pill combinations thanks to the synergistic activities of the two compounds.” They concluded with “The possibility that DPP-4i reduces the risk of G(U)TI associated with SGLT2i would make the rationale for the DPP-4i/SGLT2i combination therapy even stronger.”


Fadini GP, Bonora BM, Mayur S, Rigato M, Avogaro A. DPP-4 inhibitors moderate the risk of genitourinary tract infections associated with SGLT2 inhibitors [published online October 20, 2017]. Diabetes Obes Metab. doi:10.1111/dom.13130