Insulin Formulation Safety and Efficacy

Evidence for Reduced Use of Premixed Human Insulin

The American Diabetes Association recommends that premixed human insulin should be avoided in the hospital setting due to unacceptable hypoglycemia risk, as evidenced by a study in elderly patients (mean age ~70 years) that demonstrated a threefold higher rate of hypoglycemia compared with basal-bolus regimens using insulin analogs 1
NPH insulin has a pronounced peak of action approximately 8-12 hours after injection, creating significant hypoglycemia risk in patients with poor or variable oral intake, highlighting the need for more predictable pharmacokinetics 1

The American College of Endocrinology recommends that in people with type 1 diabetes, treatment with analog insulins is associated with less hypoglycemia and weight gain as well as lower A1C compared with human insulins, with a strength of evidence rated as high 4, 5, 3
Long-acting insulin analogs (U-300 glargine or degludec) confer lower hypoglycemia risk compared with U-100 glargine, according to the Endocrine Society 4, 3

The American Association of Clinical Endocrinologists recommends that basal insulin analogs have longer duration of action with flatter, more constant plasma concentrations and activity profiles than NPH insulin, making them a preferred choice 3, 2
For basal insulin, options include once-daily administration of glargine (U100 or U300) or degludec (U100 or U200), which are preferred over NPH, as stated by the American Diabetes Association 2

The World Health Organization recommends using human insulin to manage blood glucose in adults with type 1 and type 2 diabetes in resource-limited settings where cost is prohibitive, but notes that long-acting insulin analogues should be considered for adults with frequent severe hypoglycemia 8
Greatest caution is warranted for people at high risk of hypoglycemia, such as older patients and those with chronic kidney disease, and patient education and use of low or variable dosing may be used to mitigate hypoglycemia risk, according to the American Geriatrics Society 2