What are the American guidelines for insulin use in an adult patient with type 2 diabetes mellitus (T2DM)?

American Guidelines for Insulin Use in Type 2 Diabetes Mellitus

GLP-1 receptor agonists, including dual GIP/GLP-1 receptor agonists, are preferred over insulin for glycemic management in adults with type 2 diabetes. 1

When to Initiate Insulin Therapy

Insulin should be started immediately in the following situations, regardless of background glucose-lowering therapy or disease stage:

• Evidence of ongoing catabolism (unexpected weight loss) 1
• Symptoms of hyperglycemia are present 1
• A1C >10% (>86 mmol/mol) 1
• Blood glucose ≥300 mg/dL (≥16.7 mmol/L) 1

For patients with less severe hyperglycemia, insulin is considered when A1C is ≥7.5% after optimal use of other antihyperglycemic agents. 2

Preferred Treatment Hierarchy

Before starting insulin, prioritize the following agents based on comorbidities:

• Heart failure (HFrEF or HFpEF): SGLT2 inhibitor is recommended for glycemic management and prevention of HF hospitalizations 1
• CKD with eGFR 20-60 mL/min/1.73 m² and/or albuminuria: SGLT2 inhibitor should be used for minimizing CKD progression, reducing cardiovascular events, and reducing HF hospitalizations 1
• Advanced CKD (eGFR <30 mL/min/1.73 m²): GLP-1 RA is preferred due to lower hypoglycemia risk and cardiovascular event reduction 1

Insulin Initiation Protocol

Starting Dose

For insulin-naive patients with type 2 diabetes:

• Start with 10 units once daily or 0.1-0.2 units/kg/day of basal insulin 1, 3
• Administer at the same time each day 3
• For severe hyperglycemia (A1C ≥9%), consider higher starting doses of 0.3-0.4 units/kg/day 3

Titration Algorithm

Increase basal insulin based on fasting glucose:

• If fasting glucose 140-179 mg/dL: increase by 2 units every 3 days 3
• If fasting glucose ≥180 mg/dL: increase by 4 units every 3 days 3
• Target fasting plasma glucose: 80-130 mg/dL 3
• If hypoglycemia occurs, reduce dose by 10-20% immediately 3

Combination Therapy Recommendations

If insulin is used, combination therapy with a GLP-1 RA (including dual GIP/GLP-1 RA) is recommended for greater glycemic effectiveness, beneficial effects on weight, and reduced hypoglycemia risk. 1 Insulin dosing should be reassessed upon addition or dose escalation of a GLP-1 RA. 1

Continue metformin when initiating or intensifying insulin therapy unless contraindicated or not tolerated. 1, 3

Other glucose-lowering agents may be continued upon insulin initiation for ongoing glycemic and metabolic benefits (weight, cardiometabolic, or kidney benefits). 1

Reassess and reduce or discontinue sulfonylureas and meglitinides when starting insulin to minimize hypoglycemia risk and treatment burden. 1

Recognizing Overbasalization

Monitor for signs of overbasalization during insulin therapy:

• Basal dose exceeding 0.5 units/kg/day 1, 3
• Significant bedtime-to-morning glucose differential (≥50 mg/dL) 3
• Postprandial-to-preprandial glucose differential 1
• Occurrences of hypoglycemia (aware or unaware) 1
• High glycemic variability 1

When overbasalization is suspected, promptly reevaluate and add prandial insulin or intensify GLP-1 RA therapy rather than continuing to escalate basal insulin. 1, 3

Advancing Beyond Basal-Only Therapy

When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day, add prandial insulin rather than continuing to escalate basal insulin alone. 1, 3

Starting prandial insulin:

• Begin with 4 units of rapid-acting insulin before the largest meal 3
• Alternatively, use 10% of current basal dose 3
• Increase prandial insulin by 1-2 units or 10-15% every 3 days based on postprandial glucose readings 3

Type of Insulin

Human insulin is recommended for managing blood glucose in adults with type 2 diabetes for whom insulin is indicated. 1

Long-acting insulin analogues (glargine or detemir) may be considered for patients who have frequent severe hypoglycemia with human insulin, as they reduce severe hypoglycemic events compared to NPH insulin. 1 However, the relatively modest overall benefit from insulin analogues is outweighed by the large price difference in resource-limited settings. 1

Cost Considerations

Routinely assess all patients for financial obstacles that could impede diabetes management. 1 Clinicians should work collaboratively with diabetes care team members and social services professionals to implement strategies to reduce costs. 1

For patients with cost-related barriers, consider lower-cost medications (metformin, sulfonylureas, thiazolidinediones, and human insulin) within the context of their risks for hypoglycemia, weight gain, cardiovascular and kidney events, and other adverse effects. 1

Common Pitfalls to Avoid

Do not delay insulin initiation in patients not achieving glycemic goals with oral medications, as this prolongs exposure to hyperglycemia and increases complication risk. 3

Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to overbasalization with increased hypoglycemia risk and suboptimal control. 3

Do not abruptly discontinue oral medications when starting insulin therapy due to risk of rebound hyperglycemia. 2

Do not use sliding scale insulin as monotherapy, as scheduled basal-bolus regimens are superior. 3