What is the first line treatment for diabetes?

First-Line Treatment for Type 2 Diabetes

Metformin is the optimal first-line pharmacologic treatment for type 2 diabetes, initiated at or soon after diagnosis alongside comprehensive lifestyle modifications including diet and exercise. 1

Initial Treatment Approach

Standard First-Line Therapy

• Metformin should be started at the time of diagnosis unless contraindications exist or the patient is intolerant 1
• Begin metformin at a low dose (typically 500 mg daily) with gradual titration to minimize gastrointestinal side effects 1
• Maximum dose is 2000 mg daily in divided doses 2
• Metformin is effective, safe, inexpensive, and may reduce cardiovascular events and death 1

When Insulin Takes Priority Over Metformin

Insulin therapy must be initiated first (with metformin added later) when patients present with: 1

• Random blood glucose ≥250 mg/dL (13.9 mmol/L) 1
• A1C ≥8.5% (69 mmol/mol) 1
• Ketosis or diabetic ketoacidosis 1
• Significant hyperglycemic symptoms (polyuria, polydipsia, weight loss) 1
• A1C ≥10% (86 mmol/mol) or blood glucose >300 mg/dL (16.7 mmol/L) 1
• Evidence of ongoing catabolism (weight loss, ketonuria) 1

Once metabolic stabilization occurs with insulin, metformin should be added and insulin can potentially be tapered 1

Lifestyle Modifications Are Mandatory

• Diet and exercise remain the foundation of any type 2 diabetes treatment program and must be integrated with pharmacotherapy, not used as isolated initial treatment 1
• Lifestyle interventions should target 7-10% decrease in excess weight for overweight/obese patients 1

Metformin Contraindications and Monitoring

Renal Function Requirements

• Safe to use when eGFR ≥30 mL/min/1.73 m² 1, 2
• No dose adjustment needed when eGFR ≥60 mL/min/1.73 m² 2
• Consider dose reduction when eGFR 45-59 mL/min/1.73 m² 2
• Halve the dose when eGFR 30-44 mL/min/1.73 m² 2
• Contraindicated when eGFR <30 mL/min/1.73 m² 2

Important Monitoring

• Monitor vitamin B12 levels periodically, especially in patients on metformin for >4 years, as deficiency can worsen neuropathy symptoms 1, 2
• Monitor renal function at least annually, or every 3-6 months in patients with reduced kidney function 2

When to Intensify Beyond Metformin

• Do not delay treatment intensification if glycemic targets are not met 1
• Reassess A1C every 3 months during titration 2
• If A1C remains above target despite maximum tolerated metformin dose, add a second agent based on patient-specific factors including cardiovascular/renal comorbidities, hypoglycemia risk, weight impact, and cost 1
• Early combination therapy can be considered at treatment initiation in some patients, particularly those with baseline A1C ≥9.0% 1

Special Populations: Children and Adolescents

For youth with type 2 diabetes: 1

• Metformin is first-line when A1C <8.5% without ketosis/ketoacidosis
• Maximum dose is 2000 mg daily in divided doses for patients ≥10 years old 2
• Insulin is required first when blood glucose ≥250 mg/dL or A1C ≥8.5%, with metformin added after stabilization 1
• GLP-1 receptor agonists and SGLT2 inhibitors are now approved options for youth when metformin alone is insufficient 1

Common Pitfalls to Avoid

• Starting metformin at full dose causes intolerance - always begin low and titrate gradually 1
• Failing to check renal function before initiation - this is mandatory to prevent lactic acidosis risk 2
• Delaying treatment intensification when targets aren't met - this leads to prolonged hyperglycemia and increased complication risk 1
• Abruptly discontinuing metformin when adding insulin - continue metformin as it reduces weight gain, insulin dose requirements, and hypoglycemia 3