What is the value of faster acting prandial insulin?
Rapid acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared to regular human insulin. However, their absorption rate and time-action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk for early postmeal hyperglycemia and late postmeal hypoglycemia. Increased demand for faster acting insulins that can quickly control PPG excursions without increasing the risk for late hypoglycemia, led to the development of ultra-rapid acting insulins, including ultra rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by 2 excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently demonstrated an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart, and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 hour and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss potential benefits and considerations with URLi compared with RAIs.

Source: https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14773?af=R