Insulin Dosing: How High Can You Go?

What is the highest dose of insulin that can be used in a patient whose diabetes remains uncontrolled on a regimen of insulin plus an oral antidiabetic agent?

-- MD

When it comes to using insulin to treat hyperglycemia, “the sky’s the limit.” Extremely high doses are occasionally required; that is the reason U-500 insulin is available. A colleague once reported using 35,000 units of insulin a day in a patient with a genetic receptor defect. In patients with glucotoxicity, hyperglycemia, and down-regulation of the beta cells, very high doses of insulin are needed to reverse the clinical situation; after this has been accomplished, the insulin dose can be gradually lowered to a maintenance level. Ironically, hyperglycemia may either stimulate the beta cells to correct the clinical problem or have a toxic effect on the beta cells (ie, induce apoptosis) and thus worsen the situation.

In patients with type 2 diabetes, marked obesity, and insulin resistance, total daily insulin doses of 200 to 300 units are often required. In this setting, management for most patients includes a total of 1.0 to 2.0 units of insulin per kilogram per day; thus, in very obese patients, a larger total dose is required. In these patients-provided they have no contraindication-metformin therapy is continued by most clinicians to treat insulin resistance, improve glucose control, and minimize further weight gain.

-- Russell D. White, MD
Professor of Medicine
Director, Sports Medicine Fellowship Program
University of Missouri–Kansas City School of Medicine