What are the recommended guidelines for initiating and titrating insulin therapy in adults with type 2 diabetes (and type 1 diabetes), including dosing, titration targets, and considerations such as renal function and hypoglycemia risk?

Insulin Guidelines for Adults with Type 2 and Type 1 Diabetes

When to Start Insulin Therapy

Initiate insulin immediately in adults with type 2 diabetes when A1C >10% (>86 mmol/mol), blood glucose ≥300 mg/dL (≥16.7 mmol/L), or when symptoms of hyperglycemia (polyuria, polydipsia, weight loss) or catabolism are present. 1 This represents severe hyperglycemia requiring urgent intervention regardless of other medications.

For less severe hyperglycemia (A1C 7–10%), insulin should be considered when oral agents and GLP-1 receptor agonists fail to achieve glycemic targets after 3–6 months of optimization. 1 However, GLP-1 receptor agonists (including dual GIP/GLP-1 agonists) are preferred over insulin for most patients with type 2 diabetes due to superior cardiovascular and weight outcomes. 1

Special Population Considerations

• Heart failure: SGLT2 inhibitors are preferred first-line for glycemic management and prevention of HF hospitalizations. 1
• CKD with eGFR 20–60 mL/min/1.73 m²: SGLT2 inhibitors minimize CKD progression and reduce cardiovascular events. 1
• Advanced CKD (eGFR <30 mL/min/1.73 m²): GLP-1 receptor agonists are preferred due to lower hypoglycemia risk. 1

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Initial Insulin Dosing

Type 2 Diabetes (Insulin-Naïve)

Start with basal insulin at 10 units once daily OR 0.1–0.2 units/kg/day, administered at the same time each day. 1, 2, 3 For a 70 kg patient, this equals 7–14 units daily.

For severe hyperglycemia (A1C ≥9%, glucose ≥300 mg/dL), consider higher starting doses of 0.3–0.5 units/kg/day split 50% basal and 50% prandial (divided among three meals). 1, 2 This basal-bolus approach from the outset is appropriate when immediate aggressive control is needed.

Type 1 Diabetes

Total daily insulin requirement is 0.4–1.0 units/kg/day, with 0.5 units/kg/day typical for metabolically stable patients. 1, 2 Allocate approximately 40–50% as basal insulin (once or twice daily) and 50–60% as prandial insulin (divided among meals). 1, 2

For a 70 kg patient: Start with 35 units total daily (0.5 × 70), giving ~17 units basal and ~18 units prandial (6 units before each meal). 2

Higher doses (up to 1.5 units/kg/day) are required during puberty, pregnancy, or acute illness. 2

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Insulin Titration Protocols

Basal Insulin Titration

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

Titration schedule:

• Fasting glucose 140–179 mg/dL: Increase by 2 units every 3 days. 1, 2
• Fasting glucose ≥180 mg/dL: Increase by 4 units every 3 days. 1, 2
• If hypoglycemia (<70 mg/dL) occurs: Reduce dose by 10–20% immediately. 1, 2

Daily fasting glucose monitoring is essential during titration. 1, 2 Reassess every 3 days during active titration and every 3–6 months once stable. 2

Critical Threshold: Recognizing "Over-Basalization"

Stop escalating basal insulin when the dose exceeds 0.5 units/kg/day (approaching 1.0 units/kg/day) without achieving glycemic targets. 1, 2 At this point, add prandial insulin or a GLP-1 receptor agonist rather than further basal increases.

Clinical signals of over-basalization include: 1, 2

• Basal dose >0.5 units/kg/day
• Bedtime-to-morning glucose differential ≥50 mg/dL
• Hypoglycemia episodes despite overall hyperglycemia
• High glucose variability

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Adding Prandial Insulin

Initiate prandial insulin when: 1, 2

• Basal insulin exceeds 0.5 units/kg/day without achieving A1C goals
• Fasting glucose is controlled (80–130 mg/dL) but A1C remains above target after 3–6 months
• Significant postprandial glucose excursions (>180 mg/dL) persist

Prandial Insulin Dosing

Start with 4 units of rapid-acting insulin (lispro, aspart, or glulisine) before the largest meal, OR use 10% of the current basal dose. 1, 2

Administer rapid-acting insulin 0–15 minutes before meals for optimal postprandial control. 1, 2, 4

Prandial Insulin Titration

Target postprandial glucose: <180 mg/dL (measured 2 hours after meals). 1, 2

Increase each meal dose by 1–2 units (or 10–15%) every 3 days based on 2-hour postprandial glucose readings. 1, 2 If hypoglycemia occurs, reduce the implicated dose by 10–20% immediately. 2

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Combination Therapy Recommendations

Metformin

Continue metformin at maximum tolerated dose (up to 2,000–2,550 mg daily) when initiating or intensifying insulin therapy. 1, 2, 5 Metformin reduces total insulin requirements by 20–30% and provides superior glycemic control compared to insulin alone. 2, 5

Discontinue metformin only for specific contraindications (acute illness with renal impairment, tissue hypoxia, contrast administration). 2

GLP-1 Receptor Agonists

Combination therapy with a GLP-1 receptor agonist (including dual GIP/GLP-1 agonists) is recommended when adding insulin for greater glycemic effectiveness, beneficial effects on weight, and reduced hypoglycemia risk. 1, 3 Reassess insulin dosing upon addition or dose escalation of a GLP-1 RA. 1

When basal insulin exceeds 0.5 units/kg/day, adding a GLP-1 RA may be preferable to prandial insulin, offering comparable postprandial control with less hypoglycemia and weight gain. 1

Other Oral Agents

Reassess the need for and/or dose of sulfonylureas and meglitinides when starting insulin to minimize hypoglycemia risk. 1 Consider discontinuing sulfonylureas when advancing to basal-bolus therapy. 2

Continue other glucose-lowering agents (unless contraindicated) for ongoing glycemic and metabolic benefits (weight, cardiometabolic, kidney benefits). 1

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Special Considerations

Renal Impairment

For CKD stage 5: 2

• Type 2 diabetes: Reduce total daily insulin dose by 50%
• Type 1 diabetes: Reduce total daily insulin dose by 35–40%

For eGFR <45 mL/min/1.73 m²: Titrate conservatively and monitor closely for hypoglycemia, as insulin clearance decreases with declining kidney function. 1, 2

Hospitalized Patients

For non-critically ill hospitalized patients eating regular meals: 2

• Start with 0.3–0.5 units/kg/day total (50% basal, 50% prandial divided among three meals)
• High-risk patients (age >65, renal impairment, poor oral intake): Use 0.1–0.25 units/kg/day
• Patients on high-dose home insulin (≥0.6 units/kg/day): Reduce total daily dose by 20% upon admission

Check glucose before each meal and at bedtime. For NPO patients or those with poor intake, check every 4–6 hours and use basal-plus-correction regimen. 2

Target glucose range: 140–180 mg/dL for most non-critically ill hospitalized patients. 2

Perioperative Management

Reduce basal insulin dose by approximately 25% the evening before surgery to achieve target glucose with decreased hypoglycemia risk. 2 While NPO perioperatively, monitor glucose every 2–4 hours and treat with short- or rapid-acting insulin as needed. 2

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Hypoglycemia Management

Treat any glucose <70 mg/dL immediately with 15 grams of fast-acting carbohydrate (glucose tablets, 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

Never use rapid-acting insulin at bedtime as a sole correction dose, as this markedly raises nocturnal hypoglycemia risk. 2

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Common Pitfalls to Avoid

• Do not delay insulin initiation in patients not achieving glycemic goals with oral medications; prolonged hyperglycemia increases complication risk. 1, 2
• Do not continue escalating basal insulin beyond 0.5–1.0 units/kg/day without addressing postprandial hyperglycemia; this leads to over-basalization with increased hypoglycemia and suboptimal control. 1, 2
• Do not discontinue metformin when starting insulin unless contraindicated; this leads to higher insulin requirements and more weight gain. 1, 2
• Do not use sliding-scale insulin as monotherapy; major diabetes guidelines condemn this reactive approach as ineffective and unsafe. 2
• Do not abruptly discontinue oral medications when starting insulin; continue metformin and reassess sulfonylureas/meglitinides. 1, 4

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Monitoring and Follow-Up

• Daily fasting glucose during active titration 1, 2
• Pre-meal and 2-hour postprandial glucose when on prandial insulin 2
• HbA1c every 3 months during intensive titration 2
• Reassess insulin doses every 3 days during active titration 2
• Assess for financial obstacles routinely and implement cost-reduction strategies when needed 1, 3

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Cost Considerations

For patients with cost-related barriers, consider lower-cost options (human insulin, NPH) within the context of hypoglycemia risk, weight gain, and cardiovascular/kidney outcomes. 1, 3 However, long-acting insulin analogs (glargine, detemir, degludec) reduce nocturnal hypoglycemia compared to NPH and may be considered for patients with frequent severe hypoglycemia. 1, 3, 5

Human insulin is recommended by the American College of Physicians for managing blood glucose in adults with type 2 diabetes for whom insulin is indicated. 3