Humulin R U500 Dosing

This simple calculator estimates the dose of Humulin R U500 insulin from the total daily dose of insulin.

  • Check HBA1C at the time of the switch from U100 to U500 insulin
  • If HBA1C is >8%; give 100% of the dose
  • If HBA1C is <8%, give 80% of the dose
  • Start either 60:40% or 40:30:30

Humulin R U500 Dosing Calculator

Converting U100 to U500 insulin Calculator

humulin r u500 insulin

Determining the starting dose

These are approximate values. Remember that the Humulin R U500 insulin pen has 5 unit increments/decrements. Always round to the closest 5 units when making dose suggestions


Thrice Daily Dosing

Suitable for patients who have three meals per day


Twice Daily Dosing

Suitable for patients who have two meals per day


Clinical trial evidence

The classic Hood study (reference to the first author) serves as the basis for transitioning from conventional U100 insulin injections to U500 insulin.

Study title: Two treatment approaches for human regular u-500 insulin in patients with type 2 diabetes not achieving adequate glycemic control on high dose u-100 insulin therapy with or without oral agents: a randomized, titration-to-target clinical trial.

Rationale : This was an explanatory trial to compare the efficacy and safety of two proposed dosing regimens for human regular U-500 insulin (U-500R 500units per mL) in insulin-resistant T2DM patients with a high total daily dose of insulin requirements who remain inadequately controlled.

Study Methodology

  • Type 2 diabetes mellitus patients aged 18-75 years
  • HbA1c ≥7.5-12%
  • On multiple daily insulin injections with an estimated total daily dose of insulin (TDDi) of 201-600units/day

The starting dose of U500 insulin was based on average plasma glucose (self-monitoring of plasma glucose) and the pre-initiation A1C.

  • U500-R dose is 100% of the U-100 dose if A1C > 8% or SMPG >183mg/dl
  • U500-R dose is 80% of the U-100 dose if A1C < 8% or SMPG <183mg/dl

Participants were then randomized to the dosing schedule as follows.

  • Humulin R U500 insulin is scheduled as 40:30:30 % of the total daily dose administered at breakfast, lunch and supper
  • 60:40% of the total daily dose is administered at breakfast and supper.

Outcome : A1C reduction was -1.12% and -1.22% between the study arms.  Both arms demonstrated significant reductions in A1C (compared to baseline).  Equivalence (difference,−0.10%; 95% CI, −0.33 to 0.12%; noninferiority margin, 0.4%). There were comparable requirements in TDD of U500-R at the end of the study. Furthermore, severe hypoglycemia events and weight gain were similar in both groups.

 Practice changing pearls

  • The titration algorithm for U-500R used in this trial is based on plasma equivalent glucose doses (Maximum increase per visit was 30%/day; maximum decrease per visit was 20%/day)
  • U500-R using an algorithm based approach improves glycemic control and is more convenient (less daily injections compared to conventional intensive insulin therapy) for patients on high dose U-100 insulin. A summary of the study (infographic available here)

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The MyEndoconsult Team. A group of physicians dedicated to endocrinology and internal medicine education.

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