Cranberry Proanthocyanidins and Lactobacilli for Recurrent UTI Prevention in Type 2 Diabetes

Women with type 2 diabetes mellitus (T2DM) are disproportionately affected by recurrent urinary tract infections due to glucosuria, impaired innate immune defenses, and urogenital dysbiosis, which is often compounded by the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors.

This prospective, open-label, single-arm feasibility study was conducted at the National Institute of Endocrinology in Tbilisi, Georgia. Eligible participants were women aged 40 to 75 years with established T2DM (HbA1c 6.5%-10.0%) and a confirmed history of recurrent UTIs (defined as >=2 episodes in the prior 12 months or >=1 in the prior 6 months) without active infection at enrollment.

The study protocol comprised:

• Screening window: up to 14 days to confirm eligibility and baseline stability.
• Active intervention phase: 60 consecutive days of oral supplementation with a commercial capsule containing 72 mg of standardized cranberry PACs and 2x10^9 CFU of a multi-strain Lactobacillus formulation (L. rhamnosus, L. acidophilus, L. casei) taken twice daily with meals (total 144 mg PACs daily).
• Observation phase: 120 days of prospective follow-up without study supplementation.

Standard glucose-lowering therapies (including metformin and SGLT2 inhibitors) were maintained unchanged throughout the 180-day study. The study was designed to generate operational, safety, and preliminary signal data to inform the sample size calculation and methodological design of a future randomized, double-blind, placebo-controlled clinical trial.

Inclusion criteria

• Female patients aged 40 to 75 years.
• Established diagnosis of type 2 diabetes mellitus for >= 12 months.
• Baseline glycated hemoglobin (HbA1c) between 6.5% and 10.0%.
• Documented history of recurrent urinary tract infections (>= 2 episodes in the preceding 12 months or >= 1 episode in the preceding 6 months).
• Absence of active symptomatic UTI at enrollment, verified by screening urine analysis and culture.
• Maintained on stable glucose-lowering therapy for at least 3 months prior to enrollment.
• Willing and able to comply with the 60-day supplementation and 180-day follow-up protocol.
• Provided written informed consent.

Exclusion criteria

• Active, symptomatic urinary tract infection at the time of screening.
• Known anatomical or functional urinary tract abnormalities (e.g., neurogenic bladder, urinary tract obstruction, indwelling catheter).
• Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or end-stage renal disease.
• Severe hepatic impairment or active malignancy.
• Routine use of systemic antibiotic prophylaxis for UTI within 30 days prior to screening.
• Regular intake of cranberry-containing supplements, D-mannose, or commercial probiotic formulations within 30 days prior to enrollment.
• Known allergy or hypersensitivity to cranberry extracts, proanthocyanidins, or any excipient in the study formulation.
• Pregnancy, lactation, or women planning pregnancy during the study duration.