What are the different types of Metformin (biguanide)?

Types of Metformin (Biguanide)

Metformin is available in two primary formulations: immediate-release (IR) and extended-release (ER) forms, with the extended-release versions offering once-daily dosing and potentially improved gastrointestinal tolerability compared to immediate-release formulations. 1

Immediate-Release Metformin

• Standard immediate-release (IR) tablets:
  • Typically administered twice daily with meals
  • Available in multiple dosage strengths: 500 mg, 850 mg, and 1000 mg tablets 1
  • Starting dose usually 500 mg or 850 mg once daily, gradually titrated to target dose
  • Maximum daily dose: 2,550 mg in the US and 3,000 mg in the European Union 1
  • Requires more frequent dosing (usually twice daily) compared to extended-release formulations

Extended-Release Metformin

• Extended-release (ER/XR) tablets:
  • Allows for once-daily administration, though some formulations can be given twice daily 1
  • Available in 500 mg and 1000 mg dosage strengths 2
  • Uses different proprietary delivery technologies:
    • GelShield Diffusion System (Glucophage XR) 3
    • Gastric Retention System (Glumetza) 4, 5
    • Smartcoat delivery technology (for 1000 mg Glumetza tablets) 4
  • Starting dose typically 500 mg once daily with evening meal, gradually titrated upward
  • Maximum daily dose similar to immediate-release formulation

Key Differences Between Formulations

1. Dosing frequency:

   • IR: Typically twice daily with meals
   • ER: Once daily (usually with evening meal)

2. Gastrointestinal tolerability:

   • Both formulations can cause gastrointestinal side effects (bloating, abdominal discomfort, diarrhea)
   • ER formulations may have improved GI tolerability profile compared to IR formulations 3
   • In patients who experience GI side effects with IR formulation, switching to ER may reduce these effects 3

3. Efficacy:

   • Both formulations are equally effective in glycemic control 1
   • No consistent differences in overall side effect profiles between the formulations 1

Clinical Considerations

• Dose titration: For both formulations, gradual dose titration is recommended to minimize gastrointestinal side effects 1

• Kidney function: Metformin (both formulations) should not be used in patients with eGFR <30 mL/min/1.73m² and dose reduction should be considered when eGFR is <45 mL/min/1.73m² 1

• Monitoring: Regular monitoring of vitamin B12 levels is recommended with long-term use of either formulation due to potential deficiency 1

• Cost considerations: Immediate-release metformin is generally less expensive than extended-release formulations 1

Practical Prescribing Points

• For patients with significant gastrointestinal intolerance to immediate-release metformin, switching to extended-release formulation may improve tolerability while maintaining efficacy 3

• Extended-release formulations may improve medication adherence due to once-daily dosing

• Both formulations should be temporarily discontinued during acute illness, vomiting, dehydration, or when receiving iodinated contrast material 1

• Neither formulation should be used in patients with severe hepatic impairment or conditions that might increase risk of lactic acidosis 1