When should insulin therapy be initiated in an insulin-naive patient?

When to Start Insulin in Insulin-Naive Patients

Insulin therapy should be initiated in insulin-naive patients when they present with A1C ≥9% (≥75 mmol/mol) with symptoms of hyperglycemia, when blood glucose levels are ≥300 mg/dL (≥16.7 mmol/L), or when there is evidence of catabolism such as unexpected weight loss. 1

Initial Assessment for Insulin Initiation

• Insulin should be considered as first-line injectable therapy when there is evidence of ongoing catabolism, symptoms of hyperglycemia, very high A1C levels (>10% [86 mmol/mol]), or blood glucose levels >300 mg/dL (16.7 mmol/L) 1, 2
• For patients with marked hyperglycemia (blood glucose ≥250 mg/dL [13.9 mmol/L], A1C ≥8.5% [69 mmol/mol]) who are symptomatic with polyuria, polydipsia, nocturia, and/or weight loss, basal insulin should be initiated while metformin is started and titrated 1
• In patients with ketosis/ketoacidosis, treatment with subcutaneous or intravenous insulin should be initiated to rapidly correct hyperglycemia and metabolic derangement 1
• For patients with severe hyperglycemia (blood glucose ≥600 mg/dL [33.3 mmol/L]), assessment for hyperglycemic hyperosmolar nonketotic syndrome should be considered 1

Initial Insulin Regimen Selection

• For insulin-naive patients with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs, basal insulin should be started at 0.1 to 0.2 units/kg once-daily in the evening or 10 units once- or twice-daily 3
• Basal insulin (neutral protamine Hagedorn, glargine, detemir, or degludec) is typically used with metformin and perhaps one additional noninsulin agent 1
• For patients with NPO status requiring insulin, basal insulin at 0.1-0.2 units/kg/day with correction doses of rapid-acting insulin every 4-6 hours is recommended 4

Insulin Titration Strategy

• Set fasting plasma glucose (FPG) target and choose an evidence-based titration algorithm 1
• Increase insulin dose by 2 units every 3 days to reach FPG target without hypoglycemia 1
• If hypoglycemia occurs, determine the cause; if no clear reason is identified, lower the dose by 10-20% 1
• Assess adequacy of basal insulin dose and consider clinical signals for overbasalization (e.g., basal dose more than ~0.5 units/kg/day, hypoglycemia, high variability) 1

Progression of Insulin Therapy

• When basal insulin has been titrated to appropriate fasting blood glucose levels but A1C remains above target, combination injectable therapy should be considered 1
• Options include adding a GLP-1 receptor agonist or prandial insulin (1-3 injections of rapid-acting insulin administered before meals) 1
• For patients treated with basal insulin who do not meet glycemic targets, progress to multiple daily injections with basal and premeal bolus insulins 1
• Twice-daily premixed insulin analogues may also be considered, though their pharmacodynamic profiles make them suboptimal for covering postprandial glucose excursions 1

Special Considerations

• Short-term intensive insulin therapy (STII) may be beneficial for newly diagnosed patients with high A1C (>9%), potentially improving β-cell function and achieving remission rates of 42-66% at various follow-up points 5
• Predictors of successful remission with STII include shorter diabetes duration (<2 years), lower baseline fasting glucose, higher BMI, and better early-phase insulin secretion 5
• In patients initially treated with insulin and metformin who meet glucose targets based on home blood glucose monitoring, insulin can be tapered over 2-6 weeks by decreasing the insulin dose by 10-30% every few days 1
• For youth with marked hyperglycemia (A1C ≥8.5% [69 mmol/mol]) who are symptomatic, basal insulin should be initiated while metformin is started and titrated 1

Monitoring and Adjusting Therapy

• A1C should be measured every 3 months to assess glycemic control 1
• For most adults with diabetes, target A1C is <7% (53 mmol/mol), though more stringent targets may be appropriate for selected individuals if achievable without significant hypoglycemia 1
• Less stringent A1C goals may be appropriate for patients with history of severe hypoglycemia, limited life expectancy, or extensive comorbidities 2
• Blood glucose monitoring frequency should be individualized based on the insulin regimen, with more frequent monitoring for multiple daily injection regimens 1

Common Pitfalls and Caveats

• Therapeutic inertia (delay in treatment intensification) is common and should be avoided, as it leads to prolonged periods of hyperglycemia 1
• Insulin therapy is associated with risk of hypoglycemia and weight gain; patients typically gain about 6 pounds (2.7 kg) during the first year of insulin therapy 6
• Using only sliding scale insulin without basal insulin leads to poor glycemic control and should be avoided 4
• When initiating insulin, consider continuing metformin but discontinuing sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists when more complex insulin regimens (beyond basal insulin) are used 1
• Thiazolidinediones or SGLT2 inhibitors may be continued with insulin to improve glucose control and reduce total daily insulin dose, but should be used with caution due to risk of heart failure, fractures, and weight gain (thiazolidinediones) or ketoacidosis (SGLT2 inhibitors) 1