What is the most prescribed medication for diabetes?

Metformin is the Most Prescribed Medication for Diabetes

Metformin is the most prescribed medication for diabetes due to its high efficacy, safety profile, low cost, and position as first-line therapy in all major clinical guidelines. 1, 2

Evidence Supporting Metformin as First-Line Therapy

Guideline Recommendations

• The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus report (2018) designates metformin as the first-line medication for management of type 2 diabetes 1
• The American College of Physicians (ACP) strongly recommends metformin as initial pharmacologic therapy for most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence) 1
• The ADA Standards of Medical Care (2014) states that metformin is the preferred initial pharmacological agent for type 2 diabetes 1
• The 2016 ADA Standards of Medical Care synopsis reaffirms metformin as the preferred initial pharmacologic agent (A rating) 1

Key Advantages of Metformin

1. Efficacy:

   • High efficacy in lowering HbA1c (approximately 1 percentage point reduction) 1
   • Reduces hepatic glucose output and enhances insulin sensitivity 3

2. Safety Profile:

   • Minimal hypoglycemia risk when used as monotherapy 1
   • Weight neutral or promotes modest weight loss 1, 3
   • Does not increase insulin levels (unlike secretagogues) 3

3. Cardiovascular Benefits:

   • May lower risk for cardiovascular mortality compared with sulfonylurea therapy 1
   • The UK Prospective Diabetes Study (UKPDS) demonstrated a 36% relative risk reduction in all-cause mortality and 39% reduction in myocardial infarction 3

4. Cost-Effectiveness:

   • Low cost compared to newer agents 1, 2
   • Available in generic formulations 1

5. Long-Term Safety Data:

   • Extensive clinical experience since the 1950s 3
   • Well-established safety profile 1

Metformin Formulations and Dosing

• Immediate-release formulation: Typically administered twice daily with meals 1
• Extended-release formulations: Once-daily or twice-daily administration 1, 4
• Starting dose: 500 mg once or twice daily with meals 1
• Target dose: 1,000 mg twice daily 1
• Maximum daily dose: 2,550 mg in the U.S. and 3,000 mg in the European Union 1

Contraindications and Precautions

• Renal function: Not recommended in patients with eGFR <30 mL/min/1.73m² 1, 2
• Dose reduction: Consider when eGFR is <45 mL/min/1.73m² 1, 2
• Other contraindications: Severe liver disease, alcohol abuse, heart failure, or conditions that might lead to lactic acidosis 1, 2
• Temporary discontinuation: Should be omitted during severe illness, vomiting, or dehydration 1
• Vitamin B12 monitoring: Periodic monitoring recommended due to potential for decreased serum vitamin B12 levels 1, 2

Treatment Algorithm After Metformin

When metformin monotherapy fails to achieve or maintain glycemic targets after approximately 3 months, guidelines recommend adding a second agent 1, 2:

1. Second-line options:

   • Sulfonylureas
   • Thiazolidinediones
   • DPP-4 inhibitors
   • SGLT2 inhibitors
   • GLP-1 receptor agonists
   • Basal insulin

2. Factors influencing choice of second agent:

   • Efficacy
   • Risk of hypoglycemia
   • Effect on weight
   • Side effects
   • Cost
   • Comorbidities (especially cardiovascular disease)
   • Patient preferences

Common Pitfalls to Avoid

• Delaying treatment intensification: If HbA1c targets aren't met within 3 months, therapy should be intensified 2
• Overlooking vitamin B12 monitoring: Regular monitoring is recommended, especially in patients with anemia or neuropathy 1, 2
• Inappropriate use in renal impairment: Metformin should be avoided in severe renal impairment 1, 2
• Discontinuing during illness: Metformin should be temporarily stopped during severe illness, vomiting, or dehydration to prevent lactic acidosis 1
• Not considering extended-release formulations: These may improve GI tolerability and adherence in patients who experience side effects with immediate-release formulations 4

Metformin remains the cornerstone of diabetes pharmacotherapy despite the introduction of newer agents with cardiovascular benefits, due to its proven efficacy, safety, affordability, and extensive clinical experience 5.