PEGylated insulin Lispro (LY2605541): clinical overview of a new long-acting basal insulin analog in the treatment of Type 2 diabetes mellitus

Abstract

Neutral Protamine Hagedorn insulin with an intermediate action profile has been in use for many years for the treatment of Type 1 diabetes and as an option for Type 2 diabetes. It is efficacious in reducing blood sugars, but shows substantial variability and risk of hypoglycemia. Basal insulin analogs have been developed in recent years to overcome these issues. Three basal insulin analogs are currently in the market in Europe. PEGylated insulin lispro is a new second-generation basal insulin analog which most likely will undergo review in 2016 by the US FDA and EMA in Europe for possible approval for marketing. Phase III trials are finalized, but not yet published. Phase II studies suggest antiglycemic efficacy, possible with a preferential hepato-specific action, a low rate of hypoglycemia, minor weight loss and acceptable tolerability. The benefit–risk profile needs, however, to be established.

Keywords:

• diabetes mellitus
• hypoglycemia
• insulin analog
• LY2605541
• PEGylated insulin lispro
• Type 2 diabetes

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Basal insulin has been used since 1946 (Neutral Protamine Hagedorn insulin). Insulin is effective in reducing hemoglobin A1c in both Type 1 and Type 2 diabetes.

• The major limitations with insulin therapy are hypoglycemia, complex regimen, injection frequency and weight gain.

• Two first-generation basal insulin analogs, insulin detemir and insulin glargine, and one second-generation analog, insulin degludec, are currently on the market.

• Several biosimilars and other formulations of the insulin analogs are under investigation.

• PEGylated insulin lispro is expected to be the next second-generation insulin analog on the market.

• Phase I/II trials suggest PEGylated insulin lispro to be well tolerated, efficacious, and suggests a hepato-preferential effect and associated with weight loss.

• Phase III studies in patients with Type 2 diabetes are finalized, but not yet published.

• PEGylated insulin lispro can be administered once daily.

• Further evaluation of the benefit–risk profile needs to be determined in larger trials.