What is the recommended dosing and administration schedule for 70/30 insulin (Novolin 70/30 or Humulin 70/30) in a patient with diabetes?

70/30 Insulin Dosing and Administration

For patients with type 2 diabetes requiring insulin therapy, 70/30 premixed insulin (Novolin 70/30 or Humulin 70/30) should be initiated at 12 units before dinner OR 0.2 units/kg/day split as two-thirds before breakfast and one-third before dinner, always in combination with metformin. 1, 2

Initial Dosing Strategy

Start with one of two approaches:

• Single daily injection: 12 units administered 30 minutes before dinner 2
• Twice-daily regimen: 0.2 units/kg/day total, with 2/3 of the dose before breakfast and 1/3 before dinner 1, 2

For insulin-naïve patients, an alternative starting point is 10 units or 0.1-0.2 units/kg body weight per day, divided into two equal doses administered 30 minutes before breakfast and dinner 1. The human regular/NPH 70/30 formulation must be given 30 minutes before meals, while analog versions (like Humalog Mix25) can be administered just 5-10 minutes before eating 3.

Medication Adjustments Required

Continue metformin throughout insulin therapy unless contraindicated, as this combination reduces all-cause mortality and cardiovascular events in overweight patients with diabetes 2, 4. Discontinue sulfonylureas immediately when starting 70/30 insulin to prevent additive hypoglycemia risk 2. DPP-4 inhibitors should also be stopped when using intensive insulin regimens 2.

Titration Protocol

Adjust doses every 2 weeks based on self-monitoring of blood glucose with the following algorithm 1:

• Target fasting blood glucose: 90-150 mg/dL 1
• If ≥50% of fasting values exceed goal: Increase dose by 2 units 1
• If >2 fasting values/week are <80 mg/dL: Decrease dose by 2 units 1
• If hypoglycemia occurs without clear cause: Reduce the corresponding dose by 10-20% immediately 2

Patients with type 2 diabetes commonly require ≥1 unit/kg/day or higher, which is substantially more than type 1 diabetes requirements 1.

Critical Threshold: When to Stop Escalating

When the basal insulin component exceeds 0.5 units/kg/day, stop increasing 70/30 insulin and consider alternative strategies rather than continuing to escalate the premixed formulation 1, 2. Clinical signals that you've reached this threshold include 2:

• Basal dose >0.5 units/kg/day
• Bedtime-to-morning glucose differential ≥50 mg/dL
• Recurrent hypoglycemia
• High glucose variability

Alternative Strategies at High Doses

When 70/30 insulin alone is insufficient, consider these evidence-based options 1:

1. Add SGLT-2 inhibitor or thiazolidinedione to improve control and reduce insulin requirements
2. Transition to basal insulin plus GLP-1 receptor agonist, which provides potent glucose-lowering with less weight gain and hypoglycemia compared to intensified insulin regimens
3. Convert to basal-bolus regimen for patients needing more precise dosing control

Special Populations Requiring Lower Doses

For patients at elevated hypoglycemia risk, use lower starting doses (closer to 0.1 units/kg/day or even less) 1. High-risk populations include:

• Age >65 years 1
• Renal failure 1
• Poor oral intake 1
• History of hypoglycemia 1

Common Pitfalls to Avoid

Do not use premixed insulin in patients with unpredictable eating patterns or those requiring more precise insulin dosing, as the fixed 70/30 ratio limits flexibility 1. Do not continue escalating 70/30 indefinitely if A1C remains above target—this represents therapeutic inertia and increases hypoglycemia risk without proportional benefit 1.

Never discontinue metformin when starting insulin unless contraindicated, as the combination provides superior control with less weight gain 2, 4.

Cost Considerations

Human regular/NPH 70/30 products are significantly less expensive than rapid-acting insulin analogs, with cost savings of 30-50%, making them accessible options for cost-conscious patients 2. These can be purchased at considerably lower prices than average wholesale costs at select pharmacies 2.

Expected Outcomes

With once-daily 70/30 insulin plus metformin, expect A1C reductions of 1.1-1.3% from baseline 5. Patients achieving fasting plasma glucose <126 mg/dL experience the largest A1C decreases (approximately -2.3%) 5. Adding a third injection at lunch in patients not achieving goals on twice-daily dosing can further reduce A1C from 8.4% to 7.2%, with 58% of patients reaching A1C <7% 6.

Human insulin 30/70 given 30 minutes before meals provides adequate postprandial control, though analog premixed insulins (like Humalog Mix25) given just 5 minutes before eating show significantly lower 2-hour postprandial glucose concentrations 3.