How should I calculate and give a premixed 70/30 insulin (70% NPH, 30% regular) twice daily for a 70‑kg adult with type 2 diabetes?

How to Give 70/30 Insulin BID: Dosing Calculation and Administration

For a 70‑kg adult with type 2 diabetes, start 70/30 premixed insulin at approximately 0.1–0.2 units/kg/day total (7–14 units/day), divided as 2/3 of the dose before breakfast and 1/3 before dinner, then titrate by 2–4 units every 3 days based on fasting and pre‑dinner glucose values until targets are reached.

Initial Dose Calculation

• Calculate total daily dose (TDD): Begin with 0.1–0.2 units/kg/day for insulin‑naïve patients with type 2 diabetes; for a 70‑kg adult, this equals 7–14 units/day total 1.
• Divide the TDD using a 2/3 : 1/3 split: Give 2/3 of the total dose before breakfast and 1/3 before dinner 1, 2.
  • Example: If TDD = 12 units, give 8 units before breakfast and 4 units before dinner 1, 2.
• Timing of administration: Inject 70/30 insulin 30 minutes before breakfast and 30 minutes before dinner to allow the regular insulin component to begin acting before the meal 3, 4.

Rationale for the 2/3 : 1/3 Split

• The 2/3 morning dose accounts for greater daytime insulin requirements and provides both basal coverage through the day and prandial coverage for breakfast and lunch 2.
• The 1/3 evening dose provides prandial coverage for dinner and basal insulin overnight, while reducing the risk of nocturnal hypoglycemia due to greater insulin sensitivity during sleep 2.
• Do not give equal morning and evening doses; the 2/3 : 1/3 ratio is specifically designed to match physiological insulin needs and minimize hypoglycemia risk 2.

Titration Protocol

• Increase the morning dose by 2 units every 3 days if pre‑lunch or pre‑dinner glucose remains ≥ 180 mg/dL 1, 5.
• Increase the evening dose by 2 units every 3 days if fasting glucose remains ≥ 180 mg/dL 1, 5.
• Target fasting glucose: 80–130 mg/dL (4.4–7.2 mmol/L) 1, 6.
• Target pre‑meal glucose: 80–130 mg/dL 1, 5.
• If hypoglycemia occurs (glucose < 70 mg/dL), reduce the implicated dose by 10–20 % immediately 5.

Monitoring Requirements

• Check fasting glucose daily to guide evening‑dose adjustments 1, 6.
• Check pre‑lunch and pre‑dinner glucose to guide morning‑dose adjustments 1, 6.
• Measure HbA1c every 3 months during titration to assess overall control 5.
• More frequent monitoring is required during the first 2–4 weeks after starting 70/30 insulin to detect hypoglycemia and ensure adequate dose escalation 6.

Combination with Metformin

• Continue metformin at the maximum tolerated dose (up to 2,000–2,550 mg/day) when starting 70/30 insulin; metformin reduces total insulin requirements by 20–30 % and provides superior glycemic control versus insulin alone 5, 4.
• Do not discontinue metformin when initiating insulin unless contraindicated 5.

Advantages and Limitations of 70/30 Insulin

Advantages

• Fewer daily injections: 70/30 insulin provides both basal and prandial coverage with only two injections per day, simplifying the regimen compared with separate basal and bolus injections 6, 3.
• Improved postprandial control: Premixed insulin analogues (e.g., biphasic insulin aspart 70/30) achieve twice the peak insulin levels in half the time compared with premixed human insulin 70/30, resulting in better postprandial glucose control 3, 7.
• Comparable HbA1c reduction: Studies show that 70/30 insulin reduces HbA1c by 1.1–1.3 % over 12–16 weeks, similar to other insulin regimens 4, 8.

Limitations

• Less dosing flexibility: The fixed 70 % NPH / 30 % regular ratio cannot be adjusted independently, limiting the ability to fine‑tune basal versus prandial coverage 6.
• Requires consistent meal timing: Premixed insulin regimens demand more consistent meal timing and carbohydrate intake to avoid hypoglycemia 6.
• Higher hypoglycemia risk in hospitalized patients: Randomized trials show that premixed 70/30 insulin causes a 64 % hypoglycemia rate versus 24 % with basal‑bolus therapy in hospitalized patients, leading to early trial termination; therefore, 70/30 insulin is contraindicated in the hospital setting 5.

When to Transition to Basal‑Bolus Therapy

• Consider switching to basal‑bolus insulin when the total daily dose of 70/30 insulin exceeds 0.5 units/kg/day (≈ 35 units for a 70‑kg adult) without achieving HbA1c goals 5.
• Transition is also indicated when fasting glucose is controlled but HbA1c remains above target after 3–6 months, or when meal timing becomes too variable for premixed insulin 6.
• Basal‑bolus therapy provides greater flexibility for adjusting basal and prandial insulin independently, allowing for more precise glucose control 5, 6.

Common Pitfalls to Avoid

• Do not convert on a 1:1 basis from other insulin regimens; always reduce the total dose to 80 % of the previous regimen when switching to 70/30 insulin to avoid hypoglycemia 6, 2.
• Do not use equal morning and evening doses; the 2/3 : 1/3 ratio is essential to match physiological insulin needs and reduce nocturnal hypoglycemia 2.
• Do not neglect monitoring during the transition period; frequent glucose checks are required to detect hypoglycemia and guide dose adjustments 6.
• Do not use 70/30 insulin in hospitalized patients; the high hypoglycemia rate makes it unsafe in the inpatient setting 5.
• Do not delay insulin initiation in patients not achieving glycemic goals with oral agents alone; prolonged hyperglycemia increases complication risk 5.

Expected Clinical Outcomes

• HbA1c reduction: Patients starting 70/30 insulin can expect an HbA1c reduction of 1.1–1.3 % over 12–16 weeks 4, 8.
• Fasting glucose reduction: Fasting plasma glucose typically decreases by 28–37 % from baseline 4.
• Postprandial glucose control: Premixed insulin analogues reduce postprandial glucose excursions more effectively than NPH insulin alone, with mean postprandial glucose decreases of 1.26–1.33 mmol/L after breakfast and dinner 7.
• Hypoglycemia incidence: In outpatient studies, < 2 % of patients experience major hypoglycemia and ≈ 33 % report minor hypoglycemic episodes with 70/30 insulin, comparable to NPH insulin alone 3, 7.