What is the recommended approach for prescribing oral hypoglycemic agents (OHAs) to patients with type 2 diabetes mellitus (T2DM)?

Prescribing Oral Hypoglycemic Drugs for Type 2 Diabetes

Metformin should be prescribed as the first-line oral hypoglycemic agent for most patients with type 2 diabetes mellitus (T2DM), starting at a low dose of 500 mg once or twice daily with meals and gradually titrating to an effective dose of 1000-2000 mg daily. 1, 2

Initial Therapy Selection

First-Line Therapy: Metformin

• Start at 500 mg once or twice daily with meals
• Gradually increase to target dose of 1000-2000 mg daily (maximum 2550 mg in US)
• Use extended-release formulation for once-daily dosing if adherence is a concern 3
• Monitor for gastrointestinal side effects (bloating, abdominal discomfort, diarrhea)
• Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²), severe liver disease, or history of lactic acidosis 1, 2
• Monitor vitamin B12 levels periodically, especially in patients with anemia or peripheral neuropathy 1, 2

When to Consider Immediate Insulin Therapy Instead

• HbA1c >10% or blood glucose >300 mg/dL
• Patient has marked symptoms (polyuria, polydipsia)
• Evidence of catabolism (unexpected weight loss)
• Presence of diabetic ketoacidosis 1

Treatment Intensification

When to Add a Second Agent

• If HbA1c target not achieved after 3 months of maximum tolerated metformin dose 1
• If patient presents with HbA1c ≥1.5% above individualized target 1

Second-Line Options (Consider These Factors)

1. Cardiovascular Disease Status:

   • For patients with established atherosclerotic cardiovascular disease, heart failure, or CKD: Add SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit 1

2. Weight Considerations:

   • For weight loss: GLP-1 receptor agonist (most effective) or SGLT2 inhibitor 1, 2
   • Weight neutral: DPP-4 inhibitors 1
   • Weight gain risk: Sulfonylureas, thiazolidinediones, insulin 1

3. Hypoglycemia Risk:

   • Low risk: SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, thiazolidinediones 1
   • High risk: Sulfonylureas, insulin 1

4. Cost Considerations:

   • Lower cost: Sulfonylureas 1, 2
   • Higher cost: DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists 1, 2

Specific Second-Line Medications

Sulfonylureas (e.g., Glyburide)

• Starting dose: 2.5-5 mg daily (1.25 mg for sensitive patients) 4
• Take with breakfast or first main meal
• Monitor for hypoglycemia and weight gain 1
• Use with caution in elderly or those with renal/hepatic impairment 4

SGLT2 Inhibitors (e.g., Canagliflozin)

• Starting dose: 100 mg once daily before first meal 5
• Can increase to 300 mg daily if needed and eGFR ≥60 mL/min/1.73m²
• Not recommended for glycemic control if eGFR <30 mL/min/1.73m² 1, 5
• Monitor for genital mycotic infections, volume depletion, and ketoacidosis 5

GLP-1 Receptor Agonists

• Preferred over insulin when possible for additional glucose lowering 1
• Available as daily or weekly injections
• Monitor for gastrointestinal side effects (nausea, vomiting) 1

DPP-4 Inhibitors

• Well-tolerated with low hypoglycemia risk
• Weight neutral but less potent than other options 1

Thiazolidinediones

• Monitor for edema, heart failure risk, and weight gain 1

Triple Therapy and Beyond

If dual therapy fails to achieve glycemic targets after 3 months:

• Progress to triple therapy (metformin plus two other agents) 1
• Consider insulin therapy, especially if symptoms are significant or HbA1c remains significantly elevated 1

Common Pitfalls to Avoid

1. Delaying treatment intensification - If HbA1c target not achieved after 3 months on current therapy, promptly intensify treatment 1, 2

2. Discontinuing metformin - Continue metformin when adding other agents unless contraindicated 1, 2

3. Ignoring renal function - Adjust medication dosing based on eGFR; avoid metformin if eGFR <30 mL/min/1.73m² 1

4. Overlooking vitamin B12 monitoring - Regularly check B12 levels in patients on long-term metformin therapy 1, 2

5. Neglecting cardiovascular risk - For patients with established cardiovascular disease, prioritize agents with proven cardiovascular benefits 1

6. Inappropriate sulfonylurea use - Use with caution in elderly patients or those at high risk for hypoglycemia 4

7. Not considering medication costs - Factor in affordability, especially for long-term therapy 2