In type 2 diabetes, when should insulin therapy be initiated and how should basal insulin be started and titrated, including dosing, glucose targets, and adjustments for special populations such as the elderly, renal impairment, and heart failure?

Insulin Therapy in Type 2 Diabetes: Initiation, Titration, and Management

When to Initiate Insulin Therapy

Insulin should be started immediately when HbA1c ≥9% with symptoms, blood glucose ≥300-350 mg/dL, or when there is evidence of catabolism (weight loss, ketonuria). 1, 2 For less severe hyperglycemia, insulin is indicated when HbA1c remains >7% despite optimal oral medications including metformin plus additional agents. 1, 2

Specific Initiation Criteria

• HbA1c ≥10% with symptomatic or catabolic features: start basal-bolus insulin immediately 1, 2
• HbA1c 8.5-10%: initiate basal insulin while continuing metformin 1, 2, 3
• Blood glucose ≥300-350 mg/dL: immediate insulin therapy required 1, 2
• Suspected type 1 diabetes, underweight patients, or acute illness: insulin is the preferred agent 1

Before insulin initiation, GLP-1 receptor agonists should be considered in all patients without contraindications, as they allow lower glycemic targets with lower injection burden and reduced hypoglycemia risk. 1

Starting Basal Insulin: Dosing and Administration

Initial Dose Selection

For insulin-naïve patients with type 2 diabetes, start with 10 units once daily OR 0.1-0.2 units/kg/day, administered at the same time each day. 1, 2 For a 50 kg patient, this translates to approximately 10 units daily. 2

For severe hyperglycemia (HbA1c ≥9% or glucose ≥300 mg/dL), consider higher starting doses of 0.3-0.5 units/kg/day as total daily insulin, using a basal-bolus regimen from the outset. 1, 2

Preferred Insulin Formulations

Basal insulin analogue formulations (glargine, detemir, degludec) are preferred over NPH insulin because of reduced hypoglycemia risk, particularly nocturnal hypoglycemia, when titrated to the same fasting glucose target. 1 These can be administered at any time of day with newer analogues, though bedtime dosing is traditional. 1

Continuation of Oral Medications

Metformin must be continued at maximum tolerated dose (up to 2000-2550 mg daily) when starting insulin, as this combination reduces total insulin requirements by 20-30% and provides superior glycemic control. 1, 2, 3 Sulfonylureas should be discontinued once insulin is started to prevent additive hypoglycemia risk. 1, 2

Basal Insulin Titration Protocol

Standard Titration Algorithm

Increase basal insulin by 2 units every 3 days if fasting glucose is 140-179 mg/dL. 1, 2

Increase basal insulin by 4 units every 3 days if fasting glucose is ≥180 mg/dL. 1, 2

Target fasting glucose: 80-130 mg/dL. 1, 2

If hypoglycemia occurs (glucose <70 mg/dL) without clear cause, reduce the dose by 10-20% immediately. 1, 2

Patient Self-Titration

Most patients can be taught to uptitrate their own insulin dose, typically adding 1-2 units (or 5-10% for higher doses) once or twice weekly if fasting glucose levels remain above target. 2 Daily self-monitoring of fasting blood glucose is essential during titration. 1, 2

Critical Threshold: Recognizing Over-Basalization

When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day, STOP further basal escalation and add prandial insulin instead. 1, 2 Continuing to increase basal insulin beyond this threshold leads to "over-basalization" with increased hypoglycemia risk without improved control. 1, 2

Clinical signals of over-basalization include:

• Basal dose >0.5 units/kg/day 1, 2
• Bedtime-to-morning glucose differential ≥50 mg/dL 1, 2
• Hypoglycemia episodes 1, 2
• High glucose variability 1, 2

Adding Prandial (Mealtime) Insulin

When to Add Prandial Insulin

Add prandial insulin when:

• Basal insulin has been optimized (fasting glucose 80-130 mg/dL) but HbA1c remains above target after 3-6 months 1, 2
• Basal insulin dose approaches 0.5-1.0 units/kg/day without achieving HbA1c goal 1, 2
• Significant postprandial glucose excursions occur (>180 mg/dL) 1, 2

Starting Prandial Insulin

Begin with 4 units of rapid-acting insulin (lispro, aspart, or glulisine) before the largest meal OR 10% of the current basal dose. 1, 2 Administer 0-15 minutes before meals for optimal postprandial control. 1, 2

Prandial Insulin Titration

Increase each meal dose by 1-2 units (or 10-15%) every 3 days based on 2-hour postprandial glucose readings. 1, 2

Target postprandial glucose: <180 mg/dL. 1, 2

If additional meals require coverage, add prandial insulin sequentially to the second and third meals based on glucose patterns. 1

Alternative to Prandial Insulin

When basal insulin exceeds 0.5 units/kg/day, consider adding a GLP-1 receptor agonist instead of prandial insulin. 1, 2 This combination provides comparable or better HbA1c reduction with lower hypoglycemia risk and weight loss rather than weight gain. 1, 2

Special Populations

Elderly Patients (>65 Years)

Start with lower doses (0.1-0.25 units/kg/day) to minimize hypoglycemia risk due to increased insulin sensitivity. 2 Consider a less aggressive HbA1c target of <8.0% rather than <7.0% for elderly patients with multiple comorbidities, cognitive impairment, or limited life expectancy. 2

Renal Impairment

For patients with eGFR <60 mL/min/1.73 m², start with 0.1-0.25 units/kg/day and increase glucose monitoring, as insulin clearance is reduced. 2

For CKD Stage 5:

• Type 2 diabetes: reduce total daily insulin dose by 50% 2
• Type 1 diabetes: reduce total daily insulin dose by 35-40% 2

Titrate conservatively in patients with eGFR <45 mL/min/1.73 m² to avoid hypoglycemia. 2

Heart Failure

Lower starting doses (0.1-0.25 units/kg/day) are recommended for patients with heart failure or poor oral intake to prevent hypoglycemia. 2 Monitor for fluid retention, particularly if thiazolidinediones are also used. 4

Hospitalized Patients

For hospitalized patients who are insulin-naïve or on low-dose insulin, start with a total daily dose of 0.3-0.5 units/kg/day, with half as basal insulin. 2

For patients on high-dose home insulin (≥0.6 units/kg/day), reduce the total daily dose by 20% upon hospitalization to prevent hypoglycemia. 2

For high-risk hospitalized patients (elderly, renal failure, poor oral intake), use lower doses of 0.1-0.25 units/kg/day. 2

Glucose Monitoring Requirements

Daily fasting blood glucose monitoring is essential during the titration phase. 1, 2 Patients should check fasting glucose every morning and adjust accordingly. 2

When prandial insulin is added:

• Check pre-meal glucose before each meal to calculate correction doses 2
• Obtain 2-hour postprandial glucose after each meal to assess prandial adequacy 2
• Check bedtime glucose to evaluate overall daily pattern 2

Reassess HbA1c every 3 months during intensive titration, then every 6 months once stable. 2, 3

Hypoglycemia Management

Treat any glucose <70 mg/dL immediately with 15 grams of fast-acting carbohydrate (4 glucose tablets or 4 oz juice), recheck in 15 minutes, and repeat if needed. 1, 2

If hypoglycemia occurs without an obvious cause, reduce the implicated insulin dose by 10-20% before the next administration. 1, 2

Scrupulous avoidance of hypoglycemia for 2-3 weeks can reverse hypoglycemia unawareness if present. 2

Common Pitfalls to Avoid

Do NOT delay insulin initiation in patients not achieving glycemic goals with oral medications. 1, 2 Prolonged hyperglycemia increases complication risk. 2

Do NOT discontinue metformin when starting insulin unless contraindicated. 1, 2, 3 This leads to higher insulin requirements and more weight gain. 2

Do NOT continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia. 1, 2 This causes over-basalization with increased hypoglycemia and suboptimal control. 1, 2

Do NOT use sliding-scale insulin as monotherapy. 2 Major diabetes guidelines condemn this reactive approach as it treats hyperglycemia after it occurs rather than preventing it. 2

Do NOT give rapid-acting insulin at bedtime as a sole correction dose. 2 This markedly raises nocturnal hypoglycemia risk. 2

Expected Clinical Outcomes

With properly implemented basal-bolus therapy, approximately 68% of patients achieve mean glucose <140 mg/dL, compared with 38% using sliding-scale insulin alone. 2

HbA1c reduction of 2-3% (or 3-4% in severe hyperglycemia) is achievable within 3-6 months with intensive insulin titration combined with metformin. 2

Properly executed basal-bolus regimens do not increase overall hypoglycemia incidence compared with inadequate approaches. 2

Insulin De-escalation (Tapering)

Once glycemic targets are met (HbA1c <7%), insulin can be tapered over 2-6 weeks by decreasing the dose 10-30% every few days while continuing metformin. 3 This is appropriate when initial hyperglycemia was driven mainly by glucose toxicity rather than absolute insulin deficiency. 3

For patients on high-dose steroids, reduce insulin by 40-60% as steroid doses are tapered or stopped. 2