New insulin preparations may be defined as those which are not of animal pancreas origin, or not modified in structure from human insulins.
Where insulin safety has been assessed it is usually against other insulins (human insulin or first generation analogues). The first exception is in UKPDS where mainly human insulin was assessed against lifestyle measures alone, but in a cohort where most of the exposure was probably sulfonylureas rather than insulin. In that context long term microvascular protection was found, and on extension study protection against myocardial infarction and perhaps death. Secondly, in ORIGIN, insulin glargine was assessed against standard of care (mainly metformin and/or sulfonylurea) and was not found to have any excess of vascular events. This was not a surprise as the circulating entity after subcutaneous glargine injection is a molecule with decreased growth factor and mitotic activity compared to human insulin. Insulin glargine has also been assessed against NPH insulin in regards of retinopathy: no differences.
Could insulin exacerbate malignancy? None of the current analogues have the receptor binding problem of B10-Asp insulin (mammary tumours in rats). Insulin has been given for 95 years by recurrent injection into subcutaneous tissue at high concentration without a single case report of a malignancy.
Insulin degludec was further assessed against insulin glargine in the DEVOTE study: no CV event differences. Severe hypoglycaemia was significantly reduced, implying that the increase in hypoglycaemia with insulin cannot be a cause of CV events.