Is Phlorizine safe to use for managing diabetes?

Phlorizin Safety for Diabetes Management

Phlorizin is not recommended for clinical use in diabetes management due to poor oral bioavailability and adverse effects, despite its glucose-lowering properties. 1

Mechanism of Action and Historical Context

• Phlorizin is a naturally occurring substance that inhibits sodium/glucose cotransporters in the intestine (SGLT1) and kidney (SGLT2), blocking reabsorption of glucose from the glomerular filtrate into systemic circulation 1
• It was discovered in the 19th century and demonstrated ability to induce glucosuria and reduce hyperglycemia, serving as the precursor to modern SGLT2 inhibitors (gliflozins) 2
• While phlorizin has been used as a physiological research tool, its clinical application has been limited by significant drawbacks 1

Safety Concerns with Phlorizin

• Poor oral bioavailability makes phlorizin unsuitable for clinical use in diabetes management 1
• Phlorizin lacks selectivity for SGLT2 over SGLT1, which can lead to gastrointestinal side effects 2
• There are no established clinical guidelines supporting phlorizin use in humans, as it has primarily been studied in animal models 3, 4, 5

Evidence from Animal Studies

• In streptozotocin-induced diabetic rat models, phlorizin has shown beneficial effects including:
  • Significant reduction in blood glucose levels 3
  • Improvement in lipid metabolism 3
  • Reduction in urine volume and water intake 3
  • Partial reversal of abnormal gene expression involved in hepatic glucose metabolism 4
  • Attenuation of renal injury in diabetic db/db mice 5

FDA-Approved Alternatives for Diabetes Management

Current guidelines recommend several established medication classes for diabetes management:

• First-line therapy: Metformin remains the preferred initial glucose-lowering medication for most people with type 2 diabetes 6
• Second-line options when additional therapy is needed:
  • SGLT2 inhibitors (modern derivatives that improved upon phlorizin's concept) 6
  • GLP-1 receptor agonists 6
  • DPP-4 inhibitors 7
  • Sulfonylureas 6
  • Thiazolidinediones 6
  • Insulin therapy for severe hyperglycemia 6

Special Considerations for Medication Selection

• For patients with established ASCVD, heart failure, or CKD, SGLT2 inhibitors or GLP-1 receptor agonists with proven cardiovascular benefit are recommended 6
• For older adults, medication choice should consider hypoglycemia risk, with DPP-4 inhibitors offering minimal hypoglycemia risk when used as monotherapy 6
• Cost considerations are important, especially for older adults who may be on fixed incomes and multiple medications 6

Conclusion for Clinical Practice

While phlorizin demonstrated the concept that inhibiting renal glucose reabsorption could lower blood glucose, modern SGLT2 inhibitors have been developed to overcome phlorizin's limitations. These FDA-approved medications provide the benefits of the phlorizin concept with better safety profiles, selectivity, and clinical evidence supporting their use 2, 1.

For diabetes management, clinicians should follow established guidelines using FDA-approved medications rather than considering phlorizin, which remains primarily a research tool rather than a viable clinical option 6.