When should insulin therapy be initiated in an adult with type 2 diabetes, based on HbA1c levels, symptomatic hyperglycemia, fasting plasma glucose, and special clinical circumstances?

When to Start Insulin in Type 2 Diabetes

Insulin therapy should be initiated immediately in adults with type 2 diabetes when HbA1c ≥ 10%, fasting glucose ≥ 300 mg/dL, random glucose ≥ 300–350 mg/dL with symptoms, or when ketosis/ketoacidosis is present. 1, 2, 3

Absolute Indications for Immediate Insulin Initiation

Severe Hyperglycemia with Metabolic Decompensation

• Start insulin immediately when random or fasting glucose ≥ 300 mg/dL together with catabolic features such as unintended weight loss, polyuria, polydipsia, or ketonuria. 2, 3
• HbA1c ≥ 10% (86 mmol/mol) mandates insulin therapy because oral agents lower HbA1c by only 0.9–1.1%, which is insufficient to achieve target control. 1, 4
• Patients with ketosis or ketoacidosis require immediate subcutaneous or intravenous insulin to correct hyperglycemia and metabolic derangement. 5

Symptomatic Hyperglycemia

• Youth or adults with marked hyperglycemia (blood glucose ≥ 250 mg/dL, HbA1c ≥ 8.5%) without acidosis but with symptoms of polyuria, polydipsia, nocturia, and/or weight loss should be treated initially with basal insulin while metformin is initiated and titrated. 5
• Severe hyperglycemia (blood glucose ≥ 600 mg/dL) warrants assessment for hyperglycemic hyperosmolar nonketotic syndrome and immediate insulin therapy. 5

Strong Indications for Insulin (HbA1c 9–10%)

Dual Therapy Initiation

• When HbA1c is 9–10%, the American Diabetes Association recommends initiating metformin plus basal insulin simultaneously rather than waiting for oral monotherapy to fail. 1, 2
• Start basal insulin at 10 units once daily at bedtime or 0.1–0.2 units/kg body weight (use the higher end for HbA1c ≥ 9%). 1, 6, 7
• Titrate insulin by 2–4 units every 3 days until fasting glucose reaches 80–130 mg/dL without hypoglycemia. 1, 6, 7

Metformin Must Be Continued

• Never discontinue metformin when adding insulin; it reduces insulin requirements by 20–30%, mitigates weight gain, confers cardiovascular mortality benefit, and carries minimal hypoglycemia risk. 1, 4
• Metformin is safe to continue unless eGFR falls below 30 mL/min/1.73 m². 1

Conditional Indications (HbA1c 7.5–9%)

After Oral Agent Failure

• Insulin is indicated when HbA1c ≥ 7.5% despite optimal use of oral antidiabetic medications, diet, and physical activity. 4, 7
• The preferred approach is to add basal insulin to existing metformin therapy rather than switching to insulin monotherapy. 4, 7

GLP-1 Receptor Agonist as Alternative

• For patients with HbA1c 7.5–9% who have not reached target on oral agents, a GLP-1 receptor agonist is the preferred first injectable before insulin, especially in those with cardiovascular disease or risk factors. 1
• GLP-1 agonists provide 0.6–0.8% HbA1c reduction, promote 2–5 kg weight loss, carry minimal hypoglycemia risk, and reduce cardiovascular events by 22–26%. 1

Practical Insulin Initiation Protocol

Starting Regimen

• Basal insulin: Begin with NPH, insulin glargine, or degludec at 10 units once daily at bedtime, or calculate 0.1–0.2 units/kg. 1, 6, 7
• Metformin: Start at 500 mg once or twice daily with meals; increase by 500 mg weekly to a target of 2000 mg daily (1000 mg twice daily). 1

Titration Strategy

• Increase basal insulin by 2–4 units every 3 days based on fasting glucose readings until target of 80–130 mg/dL is achieved. 1, 6, 7
• If hypoglycemia occurs, identify the cause and reduce insulin dose by 10–20%. 1

Monitoring Timeline

• Measure HbA1c at 3 months after insulin initiation; this is the longest acceptable interval before reassessing therapy. 1
• Target HbA1c is < 7% for most adults without complications. 1, 7

Intensification When Initial Therapy Fails

Adding GLP-1 Receptor Agonist

• If HbA1c remains > 7% after 3 months of optimized metformin plus basal insulin, add a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide) rather than increasing insulin dose. 1
• This provides an additional 0.6–0.8% HbA1c reduction, promotes weight loss, and has proven cardiovascular benefit. 1

Adding Prandial Insulin

• If postprandial glucose remains > 180 mg/dL despite optimized basal insulin, add rapid-acting prandial insulin starting with 4 units before the largest meal or 10% of the basal dose. 1
• Titrate prandial insulin by 1–2 units every 3 days based on 2-hour postprandial readings. 5

Special Populations

Children and Adolescents

• Youth with blood glucose ≥ 250 mg/dL and HbA1c ≥ 8.5% who are symptomatic should receive basal insulin while metformin is initiated. 5
• In pediatric patients with ketosis/ketoacidosis, insulin is mandatory; once acidosis resolves, metformin should be added while continuing subcutaneous insulin. 5

Elderly or High-Risk Patients

• For patients at high risk of hypoglycemia (advanced CKD stages 4–5, elderly with comorbidities, limited life expectancy < 10 years), target HbA1c of 7.5–8.0% rather than < 7%. 1
• Avoid sulfonylureas in older adults when adding insulin, as they increase hypoglycemia risk 7-fold. 1

Critical Pitfalls to Avoid

• Do not delay insulin when HbA1c ≥ 10% or glucose ≥ 300 mg/dL while trialing oral agents; combination therapy is required immediately. 1, 3
• Do not discontinue metformin when starting insulin unless contraindicated; it remains foundational therapy throughout intensification. 1, 4
• Do not add sulfonylureas to metformin plus insulin regimens; they markedly increase hypoglycemia risk without cardiovascular benefit. 1
• Avoid therapeutic inertia: intensify therapy within 3 months if HbA1c remains above target, as delays increase complication risk. 1
• Do not combine GLP-1 receptor agonists with DPP-4 inhibitors; no additional benefit has been demonstrated. 1