Summary: In a small exploratory study in type 2 diabetes, combining empagliflozin with linagliptin improved glucose control and shifted the urinary microbiota toward a healthy-control pattern, whereas empagliflozin alone increased some potential uropathogens; actual infection rates were not measured.
PICO Summary
| Element | Detail |
|---|---|
| Population | 30 adults with type 2 diabetes, plus 15 healthy controls; 12-week open-label randomised study, Italy. |
| Intervention | Combined empagliflozin and linagliptin, with urinary microbiota assessed by quantitative PCR and 16S rRNA sequencing. |
| Comparison | Empagliflozin alone, and untreated healthy controls. |
| Outcome | BMI fell with both treatments, but fasting glucose and HbA1c improved significantly only with the combination. At baseline, diabetes showed urinary dysbiosis. Empagliflozin alone increased total bacterial load with more Bacillota and Aerococcus, while the combination restored a microbial community resembling controls and reduced potential uropathogens. Actual urinary-infection rates were not reported. |
Expert Commentary
This is a small mechanistic study offering an intriguing hypothesis rather than practice-changing evidence, and it should be read in that spirit. The idea is biologically appealing, that the genital and urinary infection risk associated with SGLT2 inhibitors may be mediated partly through a glucose-driven shift in urinary microbiota, and that a DPP-4 inhibitor’s metabolic and immunomodulatory effects might counteract it, which the combination appeared to do by restoring a control-like community. The signal that empagliflozin alone increased certain potential uropathogens while the combination did not is hypothesis-generating and clinically interesting. I would be careful not to over-read it. With only 30 treated patients, an open-label design, 12 weeks, a single SGLT2i/DPP-4i pairing, and crucially no measurement of actual infection rates, the microbiota composition here is a surrogate, not a clinical outcome, so it cannot by itself justify adding a second drug to prevent infections. Can I use this with my patients? Not yet as a prescribing rule. It does not change the established reasons to combine these classes for glycaemic control, and the urinary-microbiome rationale for infection prevention remains an interesting lead that needs larger trials reporting real UTI outcomes before it should influence therapy.
References
Calvigioni M, Biancalana E, Rossi C, et al. Effect of SGLT2 inhibitors + DPP-4 inhibitors on urine microbiota in type 2 diabetes. Diabetes Metab Res Rev. 2026;42(1):e70127. doi:10.1002/dmrr.70127