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