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Effect of SGLT2 Inhibitors + DPP-4 Inhibitors on Urine Microbiota in Type 2 Diabetes

Calvigioni M, Biancalana E, Rossi C, Mazzantini D, Celandroni F, Ghelardi E, Solini A

Diabetes/metabolism research and reviews, 2026

30 participants

Abstract

Aims: A reduced compliance, due to urogenital minor infections, frequently compromises the clinical efficacy of SGLT2 inhibitors in subjects with type 2 diabetes (T2D). The combined use of SGLT2 inhibitors and dipeptidyl-peptidase four inhibitors seems to reduce the incidence of such side effects. We evaluated how these drugs, alone or in combination, might influence resident urinary microbiota.

Materials and methods: An open label, randomised clinical study was conducted on 30 T2D individuals for 12 weeks to compare the impact of Empagliflozin and Empagliflozin/Linagliptin on clinical parameters and urinary microbiota. Fifteen healthy individuals served as baseline controls. The composition of urinary bacterial populations was evaluated by Real-Time quantitative PCR and 16S rRNA gene sequencing.

Results: BMI was reduced by both treatments, while fasting glucose and HbA1c significantly improved only with the combination. At baseline, T2D showed a higher total bacterial load and abundance of Bacillota than controls. The prevalence and proportion of bacterial species profoundly differed between the groups, revealing a urinary dysbiosis in T2D. A different effect of Empagliflozin alone or combined with Linagliptin on microbial populations was observed: Empagliflozin increased the total bacterial load of Bacillota and Aerococcus, while the combination therapy restored a microbial community similar to that of controls, further reducing the prevalence of potential urinary…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 30 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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