For a 70‑kg adult with type 2 diabetes who only has regular (short‑acting) insulin available, how should I initiate and titrate the insulin using a twice‑daily schedule and combine it with metformin?

Using Regular Insulin in a Twice‑Daily Regimen with Metformin

For a 70‑kg adult with type 2 diabetes who only has regular insulin available, start with 10 units of regular insulin 30–45 minutes before breakfast and 10 units 30–45 minutes before dinner (total 20 units/day or 0.3 units/kg/day), combined with metformin 1000 mg twice daily, then titrate the insulin by 2–4 units every 3 days based on pre‑meal glucose readings until fasting and pre‑dinner glucose reach 80–130 mg/dL. 1

Foundation Therapy: Metformin Must Continue

• Metformin should be continued at maximum tolerated dose (up to 2000 mg daily) when adding insulin therapy, as this combination provides superior glycemic control with reduced insulin requirements and less weight gain compared to insulin alone 1, 2.
• Continue metformin 1000 mg twice daily unless contraindicated; the combination of metformin and insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia 3, 2.

Initial Dosing Strategy with Regular Insulin

• Start with 10 units of regular insulin before breakfast and 10 units before dinner (total 20 units/day or approximately 0.3 units/kg/day for a 70‑kg patient), which represents a conservative starting point for twice‑daily therapy 1, 4.
• Regular insulin must be administered 30–45 minutes before meals (not 0–15 minutes like rapid‑acting analogs) to allow adequate time for absorption and to match the postprandial glucose rise 1, 3.
• The twice‑daily schedule with regular insulin provides both basal coverage between meals and prandial coverage for the meals immediately following each injection 4.

Titration Protocol

Adjusting the Insulin Dose

• Increase each injection by 2 units every 3 days if the corresponding pre‑meal glucose is 140–179 mg/dL 1.
• Increase each injection by 4 units every 3 days if the corresponding pre‑meal glucose is ≥180 mg/dL 1.
• Target fasting glucose (which reflects the dinner dose) and pre‑dinner glucose (which reflects the breakfast dose) of 80–130 mg/dL 1.
• If hypoglycemia occurs without clear cause, reduce the implicated dose by 10–20% immediately 1.

Monitoring Requirements

• Check fasting blood glucose every morning to guide titration of the dinner dose 1.
• Check pre‑dinner glucose to guide titration of the breakfast dose 1.
• Daily self‑monitoring of blood glucose is essential during the titration phase 1.

Critical Threshold: When to Advance Beyond Twice‑Daily Regular Insulin

• When the total daily dose of regular insulin exceeds 0.5 units/kg/day (35 units/day for a 70‑kg patient) and glucose remains elevated, this signals the need for more intensive insulin coverage rather than further dose escalation 1.
• At this threshold, consider transitioning to a basal‑bolus regimen with basal insulin once daily plus rapid‑acting or regular insulin before each of three meals 1, 3.
• Clinical signals of inadequate twice‑daily coverage include persistent postprandial hyperglycemia (>180 mg/dL) despite adequate pre‑meal glucose, or HbA1c remaining above target after 3–6 months 1.

Practical Considerations for Regular Insulin

• Regular insulin has a longer duration of action (6–8 hours) compared to rapid‑acting analogs (3–5 hours), which provides some basal coverage between meals but also increases the risk of delayed hypoglycemia 3.
• The 30–45 minute pre‑meal timing is critical; administering regular insulin immediately before or after meals will result in postprandial hyperglycemia followed by delayed hypoglycemia 1, 3.
• Patients must maintain consistent meal timing and carbohydrate content to match the fixed pharmacokinetic profile of regular insulin 3.

Common Pitfalls to Avoid

• Never delay insulin initiation in patients not achieving glycemic goals with oral medications alone, as this prolongs hyperglycemia exposure and increases complication risk 1.
• Never discontinue metformin when starting insulin unless contraindicated, as this leads to higher insulin requirements and more weight gain 1, 3.
• Do not continue escalating regular insulin beyond 0.5–1.0 units/kg/day without addressing the need for more intensive insulin coverage, as this leads to overbasalization with increased hypoglycemia risk 1.
• Never administer regular insulin at bedtime as a sole correction dose, as the prolonged duration of action markedly raises nocturnal hypoglycemia risk 1.

Expected Outcomes

• With appropriate twice‑daily regular insulin combined with metformin, expect HbA1c reduction of 1.1–1.3% from baseline over 12 weeks 4.
• Fasting plasma glucose typically decreases by 28–37% from baseline with this regimen 4.
• The combination is well tolerated and allows patients to safely and effectively begin insulin therapy using a relatively simple once‑ or twice‑daily injection schedule 4.

Patient Education Essentials

• Teach proper insulin injection technique and site rotation 1.
• Provide education on recognition and treatment of hypoglycemia (treat glucose <70 mg/dL with 15 grams of fast‑acting carbohydrate) 1.
• Instruct on self‑monitoring of blood glucose and "sick day" management rules 1.
• Emphasize the importance of the 30–45 minute pre‑meal timing for regular insulin 1, 3.