Sodium-Glucose Cotransporter 2 Inhibitors and Associated Infections in Diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a novel class of oral antidiabetic agents that lower blood glucose by blocking renal glucose reabsorption in the proximal tubule, leading to glycosuria. Beyond glycaemic control, they confer cardiovascular and renal protection, yet the induced glycosuria alters the urinary milieu and predisposes patients to genitourinary infections. Genital mycotic infections, predominantly candidiasis, and urinary tract infections (UTIs) emerge as the principal infectious complications. Incidence varies by agent, dose and patient factors such as female sex, prior infection history and age. While most infections are mild and managed conservatively, they may influence adherence and prompt treatment discontinuation. Understanding the balance between metabolic benefits and infectious risk is key to optimising patient selection, counselling and monitoring strategies worldwide.

Research from Nature Portfolio

A comprehensive systematic review and meta-analysis of 77 randomised controlled trials involving over 50 000 participants revealed no significant increase in UTIs with SGLT2 inhibitors versus control (risk ratio ~1.05), but demonstrated a threefold elevation in genital mycotic infections (risk ratio ~3.30). Subgroup analyses indicated that the risk varies according to individual agents and duration of therapy. These findings, drawn from high-quality trial data, underscore the need for head-to-head comparisons of specific inhibitors to refine individual risk profiles and inform clinical decision-making.

Sodium-Glucose Cotransporter 2 Inhibitors and Associated Infections in Diabetes publication trend

The graph below shows the total number of articles in sodium-glucose cotransporter 2 inhibitors and associated infections in diabetes across all publications each year (not limited to Nature Index journals).

Technical terms

Sodium-glucose cotransporter 2 (SGLT2) inhibitor: A medication that inhibits renal glucose reabsorption in the proximal tubule, promoting urinary glucose excretion to lower blood glucose.

Glycosuria: The presence of glucose in urine, induced by SGLT2 inhibition, which creates a nutrient-rich environment favouring microbial growth.

Genital mycotic infection: A fungal infection of the genital tract, commonly due to Candida species, presenting with itching and discharge.

Urinary tract infection (UTI): A bacterial infection of the urinary system, typically involving the bladder or urethra, manifesting as dysuria, urgency and frequency.

References

1. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Scientific Reports (2017).
2. Comparative safety of different recommended doses of sodium–glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials. Frontiers in Endocrinology (2023).
3. Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation. BMJ Open Diabetes Research & Care (2020).
4. The Incidence and Risk Factors of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Using SGLT2 Inhibitors: A Real-World Observational Study. Medicines (2022).