In a 72-year-old woman weighing 81 kg who is receiving tirzepatide (Mounjaro) 12.5 mg for type 2 diabetes and will start total parenteral nutrition containing 180 g dextrose, how many units of regular insulin should be added to the TPN?

Insulin Dosing in TPN for a Patient on Tirzepatide

Start with 18 units of regular insulin added directly to the TPN bag (1 unit per 10 grams of dextrose), and monitor glucose every 4–6 hours with additional subcutaneous correction insulin as needed. This approach provides continuous basal coverage matched to the continuous carbohydrate infusion while accounting for the patient's existing GLP-1 receptor agonist therapy.

Initial Insulin Calculation for TPN

• For patients receiving continuous parenteral nutrition, add 1 unit of regular insulin for every 10 grams of dextrose to the TPN solution, particularly when more than 20 units of correctional insulin have been required in the past 24 hours. 1
• With 180 grams of dextrose in the TPN, the starting dose is 18 units of regular insulin added directly to the bag (180 g ÷ 10 = 18 units). 1
• Adding insulin directly to the parenteral nutrition bag is the safest method to prevent hypoglycemia if the TPN is stopped or interrupted unexpectedly. 1

Adjustments for Tirzepatide (Mounjaro) Therapy

• Tirzepatide 12.5 mg provides substantial glucose-lowering effects through dual GIP/GLP-1 receptor agonism, reducing HbA1c by 1.87–2.59% in clinical trials. 2, 3
• The drug increases insulin secretion, reduces glucagon release in a glucose-dependent manner, and delays gastric emptying, which will reduce overall insulin requirements compared to patients not on incretin therapy. 4
• Start at the lower end of the dosing range (1 unit per 10 g rather than 1 unit per 8–10 g) because tirzepatide's insulin-sensitizing effects will reduce exogenous insulin needs. 2, 3

Daily Titration Protocol

• Adjust the insulin dose in the TPN solution daily based on the previous 24 hours of glucose readings and correctional insulin requirements. 1
• If correctional insulin totals >20 units in 24 hours, increase the TPN insulin by 20–30% the next day (e.g., from 18 to 22–24 units). 1
• If glucose values remain >180 mg/dL consistently, increase TPN insulin by 4 units daily until fasting/pre-meal glucose reaches 80–130 mg/dL. 1
• If glucose falls <70 mg/dL, immediately reduce TPN insulin by 10–20% (approximately 2–4 units) and treat hypoglycemia with IV dextrose if the patient cannot take oral carbohydrates. 1

Subcutaneous Correction Insulin Protocol

• Administer subcutaneous regular insulin every 6 hours (or rapid-acting insulin every 4 hours) as correction doses in addition to the TPN insulin. 1
• Use a simplified correction scale: 2 units for glucose >250 mg/dL and 4 units for glucose >350 mg/dL. 1
• Correction insulin is an adjunct to the scheduled TPN insulin, not a replacement—never rely solely on sliding-scale corrections. 1

Monitoring Requirements

• Check capillary glucose every 4–6 hours during TPN administration to assess adequacy of insulin coverage. 1
• For patients with poor oral intake or NPO status receiving TPN, this 4–6 hour monitoring interval is standard. 1
• Daily fasting glucose (or pre-TPN glucose if cycled) guides the next day's TPN insulin adjustment. 1

Critical Threshold: When to Stop Escalating TPN Insulin

• If TPN insulin approaches 0.5 units/kg/day (approximately 40 units for this 81 kg patient) without achieving glucose targets, do not continue escalating—instead, reassess the TPN formulation, rule out infection/stress hyperglycemia, and consider adding basal subcutaneous insulin. 1
• Signs of "over-insulinization" include glucose variability ≥50 mg/dL between checks, any hypoglycemia, or persistently elevated glucose despite high insulin doses. 1

Special Considerations for Tirzepatide Continuation

• Continue tirzepatide during TPN therapy unless the patient develops severe nausea, vomiting, or gastroparesis that precludes subcutaneous absorption. 2, 3
• Tirzepatide's glucose-dependent mechanism means it will not cause hypoglycemia when used with appropriate insulin dosing, and it provides additional glucose-lowering without increasing hypoglycemia risk. 2, 4
• The drug's weight loss effects (6.2–12.9 kg in trials) may be attenuated during TPN, but glycemic benefits persist. 2, 3

Expected Clinical Outcomes

• With properly dosed TPN insulin plus tirzepatide, approximately 68% of patients achieve mean glucose <140 mg/dL, compared to 38% with inadequate insulin coverage. 1
• The combination of TPN insulin and tirzepatide should maintain glucose in the 140–180 mg/dL range for most non-critically ill patients. 1
• Hypoglycemia rates remain low (<1–2% of patients) when tirzepatide is combined with appropriately dosed insulin, due to its glucose-dependent mechanism. 2, 5

Common Pitfalls to Avoid

• Never use sliding-scale insulin as monotherapy for TPN patients—scheduled insulin in the TPN bag is mandatory for continuous carbohydrate infusion. 1
• Do not discontinue tirzepatide when starting TPN unless gastrointestinal side effects preclude its use; the drug reduces total insulin requirements by enhancing insulin sensitivity. 2, 3
• Avoid giving rapid-acting insulin at bedtime as a sole correction dose, as this markedly raises nocturnal hypoglycemia risk. 1
• Never completely withhold insulin if TPN is temporarily interrupted—start a 10% dextrose infusion immediately to prevent hypoglycemia and allow time to adjust insulin dosing. 1

Alternative Approach: NPH Insulin for Continuous TPN

• If regular insulin in the TPN bag is unavailable or impractical, administer NPH insulin subcutaneously every 8–12 hours to cover the continuous nutritional load. 1
• Starting dose would be 8–10 units NPH every 12 hours (approximately 1 unit per 10–12 g carbohydrate), with the same daily titration principles. 1
• This approach is less preferred because it does not automatically stop if TPN is interrupted, increasing hypoglycemia risk. 1