What is the step-by-step approach for Type 2 Diabetes Mellitus (T2DM) management with medications, including names and doses?

Step-by-Step Approach for Type 2 Diabetes Mellitus (T2DM) Management with Medications

Metformin is the preferred first-line pharmacological agent for T2DM management due to its well-established safety profile, glucose-lowering ability, weight-neutral effects, and low risk of hypoglycemia. 1

Step 1: Initial Therapy with Metformin

• Starting dose: 500 mg once or twice daily with meals
• Titration: Gradually increase to effective dose of 1000-2000 mg daily
• Maximum effective dose: 2000 mg daily 2
• Formulation option: Consider extended-release metformin for better GI tolerability and once-daily dosing 3
• Monitoring: Check vitamin B12 levels periodically, especially in patients with anemia or peripheral neuropathy 1
• Contraindications: eGFR <30 mL/min/1.73m², severe liver disease, history of lactic acidosis 1

Step 2: Treatment Intensification (If HbA1c Target Not Achieved After 3 Months)

If monotherapy at maximum tolerated dose doesn't achieve or maintain HbA1c target after 3 months, add a second agent 2:

For Patients with Established ASCVD, Heart Failure, or CKD:

• Add SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit 1
  • GLP-1 receptor agonists options:
    • Liraglutide: Start 0.6 mg daily for 1 week, then 1.2 mg daily
    • Exenatide: 5 μg twice daily for 1 month, then 10 μg twice daily
    • Lixisenatide: 10 μg daily for 2 weeks, then 20 μg daily 2
  • SGLT2 inhibitors options:
    • Empagliflozin: 10 mg daily, can increase to 25 mg daily
    • Dapagliflozin: 5-10 mg daily
    • Canagliflozin: 100 mg daily, can increase to 300 mg daily

For Patients Without Established Cardiovascular Disease:

• Options include:
  • Sulfonylureas (low cost but risk of hypoglycemia and weight gain)
  • DPP-4 inhibitors (weight neutral, low hypoglycemia risk)
  • SGLT2 inhibitors (weight loss, low hypoglycemia risk)
  • GLP-1 receptor agonists (weight loss, low hypoglycemia risk)
  • Thiazolidinediones (risk of weight gain, fluid retention) 2, 1

Step 3: Consider Insulin Therapy

Immediate Insulin Initiation Scenarios:

• Newly diagnosed T2DM patients who are symptomatic
• HbA1c ≥10%
• Blood glucose ≥300 mg/dL (16.7 mmol/L) 2

Insulin Regimens:

1. Basal insulin:

   • Starting dose: 10 units or 0.1-0.2 units/kg daily
   • Titrate by 2-4 units every 3-4 days until target fasting glucose achieved
   • Options: Glargine, Detemir, Degludec, NPH 2, 1

2. If basal insulin inadequate:

   • Option A: Add rapid-acting insulin before largest meal
   • Option B: Add GLP-1 receptor agonist
   • Option C: Switch to twice-daily premixed insulin (70/30 NPH/regular, 70/30 aspart mix, 75/25 or 50/50 lispro mix) 2

3. Multiple daily injections:

   • Basal insulin plus prandial insulin before meals
   • Starting prandial dose: 4 units or 10% of basal dose
   • Adjust based on postprandial glucose readings 2

Step 4: Short-term Intensive Insulin Therapy for Newly Diagnosed Patients

• Consider for: Newly diagnosed T2DM with HbA1c >9.0% or FPG ≥11.1 mmol/L with symptomatic hyperglycemia
• Duration: 2 weeks to 3 months
• Options:
  • Premixed human insulin or analogs (1-3 times daily)
  • Basal-bolus regimen
  • Continuous subcutaneous insulin infusion 2

Important Considerations

• Continue metformin when adding other agents unless contraindicated 1
• Monitor renal function regularly, especially with metformin use 1
• Avoid therapeutic inertia - intensify therapy when HbA1c targets are not met 1
• Manage GI side effects of metformin by using extended-release formulations and gradual dose titration 3
• For patients with multiple medications, extended-release metformin may improve adherence 3

Common Pitfalls to Avoid

• Delaying treatment intensification when targets aren't met
• Discontinuing metformin when adding other agents
• Ignoring renal function monitoring and medication dose adjustments
• Overlooking vitamin B12 monitoring in patients on long-term metformin
• Neglecting cardiovascular risk factors when selecting medications 1