When should insulin be initiated and what are the considerations for choosing an insulin regimen?

Insulin Initiation in Type 2 Diabetes

Insulin therapy should be initiated immediately in patients with type 2 diabetes who have severe hyperglycemia (blood glucose ≥300-350 mg/dL or HbA1c ≥10%), symptomatic hyperglycemia, or catabolic features such as weight loss or ketosis. 1

When to Initiate Insulin Therapy

• Insulin should be initiated without delay when patients are not achieving glycemic goals with other therapies (typically within 3 months of recognizing failure of other treatments) 1

• Immediate insulin initiation is indicated in the following scenarios:

  • HbA1c ≥9% (consider starting at this stage) 1
  • Blood glucose ≥300-350 mg/dL or HbA1c ≥10-12% 1
  • Presence of symptomatic hyperglycemia (polyuria, polydipsia, nocturia) 1
  • Catabolic features (unintentional weight loss, ketosis) 1
  • Newly diagnosed patients with severe hyperglycemia 1

• In youth with type 2 diabetes, insulin should be initiated when:

  • Blood glucose ≥250 mg/dL or HbA1c ≥8.5% 1
  • Ketosis or ketoacidosis is present 1
  • The distinction between type 1 and type 2 diabetes is unclear 1

Initial Insulin Regimen Selection

For Most Adult Patients:

• Basal insulin is the typical starting regimen:

  • Start with 10 units or 0.1-0.2 units/kg body weight 1
  • Usually combined with metformin and possibly one additional non-insulin agent 1
  • Options include NPH, glargine, detemir, or degludec 1

• For severe hyperglycemia (HbA1c >10% or blood glucose >300 mg/dL with symptoms):

  • Consider starting with basal insulin plus mealtime insulin 1
  • This more aggressive approach is preferred when catabolic features are present 1

For Youth with Type 2 Diabetes:

• Start with basal insulin at 0.5 units/kg/day while initiating or continuing metformin 1
• After resolution of ketosis/ketoacidosis, metformin can be added or continued 1
• Basal insulin can be tapered (by 10-30% every few days) if glucose targets are met with metformin 1

Insulin Intensification Algorithm

When basal insulin has been optimized but HbA1c remains above target:

1. Add GLP-1 receptor agonist to basal insulin 1

   • Reduces postprandial glucose excursions
   • Associated with weight loss and less hypoglycemia 1
   • Fixed-ratio combination products are available 1

2. Add prandial (mealtime) insulin 1

   • Start with 1-3 injections of rapid-acting insulin (lispro, aspart, or glulisine) before meals 1
   • Insulin analogues are preferred as they are faster-acting 1

3. Consider premixed insulin 1

   • Options include 70/30 aspart mix, 75/25 or 50/50 lispro mix 1
   • Usually administered twice daily (before breakfast and dinner) 1
   • May be less optimal for controlling postprandial glucose excursions 1

Medication Adjustments When Starting Insulin

• Metformin: Generally continued with insulin therapy 1
• Sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists: Usually withdrawn when more complex insulin regimens (beyond basal insulin) are used 1
• Thiazolidinediones (TZDs) or SGLT2 inhibitors: May be continued to improve glucose control and reduce total daily insulin dose 1
  • Use TZDs with caution in patients with heart failure risk 1
  • Monitor for risk of ketoacidosis with SGLT2 inhibitors 1

Overcoming Barriers to Insulin Initiation

• Address patient fears about hypoglycemia by starting with low doses and educating on monitoring 2, 3
• Discuss the progressive nature of type 2 diabetes early in the disease course 4
• Provide education on proper injection technique to reduce anxiety 2, 3
• Consider once-weekly insulin formulations (when available) to improve acceptance and adherence 2
• Emphasize that insulin therapy is not a sign of personal failure but a necessary step in disease management 2, 3

Insulin Dose Titration

• Once insulin therapy is initiated, timely dose titration is crucial 1
• Adjust both basal and prandial insulin doses based on self-monitoring of blood glucose (SMBG) levels 1
• Consider instructing patients in self-titration of insulin doses based on SMBG for improved glycemic control 1

Special Considerations

• In patients with chronic kidney disease, liver cirrhosis, or post-transplant diabetes, earlier insulin initiation may be necessary 2
• During pregnancy, insulin is often required sooner for glycemic control 2
• For patients with high cardiovascular risk, consider the cardiovascular effects of accompanying medications 1