When do you start a patient with type 2 diabetes on metformin (biguanide) or insulin therapy?

When to Start Metformin or Insulin in Type 2 Diabetes

Metformin should be started at the time of diagnosis of type 2 diabetes as first-line therapy unless contraindicated, while insulin should be initiated when patients present with marked hyperglycemia (A1C ≥10% or blood glucose ≥300 mg/dL), symptoms of hyperglycemia, or evidence of ongoing catabolism (weight loss). 1

Initial Therapy Decision Algorithm

Start with Metformin when:

• Patient is newly diagnosed with type 2 diabetes 1, 2
• No contraindications exist (normal renal function with eGFR ≥30 mL/min/1.73m²) 1, 3
• Patient can tolerate the medication (no severe GI intolerance) 1
• Patient does not have severe hyperglycemia or symptoms

Start with Insulin (with or without metformin) when:

• A1C ≥10% (86 mmol/mol) 1
• Blood glucose ≥300 mg/dL (16.7 mmol/L) 1
• Patient has symptoms of hyperglycemia (polyuria, polydipsia, weight loss) 1
• Evidence of ongoing catabolism (weight loss) 1
• Ketosis or ketoacidosis is present 1

Metformin Therapy Details

Benefits of Metformin:

• Effective glucose-lowering (can lower A1C by ~1.5%) 4
• Weight neutral or promotes modest weight loss 1, 5
• Low risk of hypoglycemia 6, 5
• Potential cardiovascular benefits 4
• Cost-effective 2

Contraindications to Metformin:

• Renal impairment (eGFR <30 mL/min/1.73m²) 1, 3
• Severe liver disease 3
• History of lactic acidosis 3
• Planned contrast imaging procedures (temporary hold) 3
• Severe acute illness, surgery, or other conditions that may affect renal function 3

Dosing and Administration:

• Start with low dose (500 mg daily) and gradually titrate to reduce GI side effects 1
• Extended-release formulation may improve GI tolerability for some patients 7
• Target dose typically 1000-2000 mg daily in divided doses 2
• Monitor for vitamin B12 deficiency with long-term use 1

Insulin Therapy Details

When to Initiate Insulin:

• Severe hyperglycemia at diagnosis 1
• Symptomatic hyperglycemia 1
• Evidence of catabolism (weight loss) 1
• When oral agents fail to achieve glycemic targets 1
• In patients with ketosis/ketoacidosis 1

Initial Insulin Regimen:

• Usually start with basal insulin at 10 U or 0.1-0.2 U/kg 1
• Can be used with metformin if not contraindicated 1
• For severe hyperglycemia with symptoms, consider basal-bolus regimen 1

Treatment Intensification

When Metformin Monotherapy Fails:

• If A1C target not achieved after approximately 3 months on metformin, add second agent 1
• Options include SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, or basal insulin 1
• For patients with established cardiovascular disease, consider SGLT2 inhibitors or GLP-1 receptor agonists with proven cardiovascular benefit 1, 2

When to Consider Dual Therapy Initially:

• A1C ≥9% (75 mmol/mol) at diagnosis 1
• For more rapid attainment of glycemic goals 1

Common Pitfalls and How to Avoid Them

1. Delaying treatment intensification: Treatment should be intensified if A1C targets are not met within 3 months 1, 2

2. Overlooking vitamin B12 monitoring: Regular monitoring of vitamin B12 levels in patients on long-term metformin therapy is recommended 1, 2

3. Failing to continue metformin when adding other agents: Metformin should be continued when other agents, including insulin, are added unless contraindicated 1

4. Not considering cardiovascular risk: In patients with established cardiovascular disease, certain agents (SGLT2 inhibitors, GLP-1 receptor agonists) may offer additional benefits beyond glucose control 1, 2

5. Inappropriate metformin use: Avoid use in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) or other contraindications 1, 3

6. Delaying insulin when needed: Early insulin initiation is crucial in patients with severe hyperglycemia, symptoms, or catabolism 1, 2