Hypoglycemia rates and incidence

*Events/patients/30 days.

Rates are geometric least squares means } SE (documented symptomatic and nocturnal) or means } SD (severe).

NOTE: During this trial, hypoglycemia was categorized as documented symptomatic, nocturnal, or severe hypoglycemia.

Documented symptomatic hypoglycemia was defined as signs or symptoms associated with hypoglycemia and a plasma glucose ≤70 mg/dL or <50 mg/dL. Nocturnal hypoglycemia was defined as documented symptomatic hypoglycemia occurring between bedtime and waking. By definition, severe hypoglycemia required assistance from another person for treatment and was accompanied by neurologic/cognitive impairment. Incidence is reported as the number of patients with at least one hypoglycemic episode.

All hypoglycemic analyses were performed using the full analysis set defined as all randomized patients receiving at least one dose of study drug.

Indication for Humulin® R U-500

Humulin R U-500 is a concentrated human insulin indicated to improve glycemic control in adults and children with diabetes mellitus requiring more than 200 units of insulin per day.
Limitations of Use: The safety and efficacy of Humulin R U-500 used in combination with other insulins, or when delivered by continuous subcutaneous infusion, has not been determined.


Humulin R U-500 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Humulin R U-500 or any of its excipients.

Hyperglycemia, Hypoglycemia, or Death Due to Dosing Errors With Vial Presentation
  • Can be life-threatening. Overdose has occurred as a result of dispensing, prescribing, or administration errors. Attention to details at all levels is required to prevent these errors.
  • Patients should be prescribed U-500 syringes for use with Humulin R U-500 vials. Do not use any other type of syringe to administer Humulin R U-500.
  • If using the Humulin R U-500 KwikPen®, patients should be counseled to dial and dose the prescribed number of units of insulin.
  • Do NOT perform dose conversion when using the Humulin R U-500 KwikPen or U-500 insulin syringe.

DO NOT transfer Humulin R U-500 from the KwikPen into any syringe for administration. Overdose and severe hypoglycemia can occur.

Never share a KwikPen or U-500 syringe between patients, even if the needle is changed, to avoid risk of transmission of blood-borne pathogens.

Hyperglycemia or Hypoglycemia With Changes in Insulin Regimen
  • Changes in insulin strength, manufacturer, type, injection site, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Any changes in insulin regimen should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. Due to reports of hypoglycemia and hyperglycemia, advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to the unaffected areas and to closely monitor blood glucose. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.
  • Hypoglycemia is the most common adverse reaction associated with insulin, including Humulin R U-500. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.
  • Increase monitoring with changes to insulin dosage, co-administered glucose-lowering medications, meal patterns, physical activity, and in patients with renal or hepatic impairment or hypoglycemia unawareness. To minimize risk of hypoglycemia, do not administer Humulin R U-500 intravenously, intramuscularly, or in an insulin pump or dilute or mix with other products, including other insulins.
  • Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.
Hypersensitivity and Allergic Reactions
  • Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Humulin R U-500. If hypersensitivity reactions occur, discontinue Humulin R U-500; treat per standard of care and monitor until symptoms and signs resolve.
  • May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
Fluid Retention and Heart Failure With Concomitant Use of Thiazolidinediones (TZDs)
  • Thiazolidinediones (TZDs) can cause dose-related fluid retention, particularly when used in combination with insulin. Observe for signs and symptoms of heart failure and consider reduction or discontinuation if heart failure occurs.
Adverse Reactions

Other adverse reactions include allergic reactions, lipodystrophy, injection site reactions, pruritus, and rash.

Drug Interactions
  • Some medications may alter glucose metabolism and may necessitate insulin dose adjustment.
  • Particularly close glucose monitoring may be required when Humulin R U-500 is co-administered with drugs such as antiadrenergic agents that can alter the signs of hypoglycemia.
HM U500 HCP ISI 15NOV2019

For more information, see Full Prescribing Information, including Patient Information and Instructions for Use for the KwikPen and vial.