Premixed insulin (75% insulin lispro protamine suspension, 25% insulin lispro) is non-inferior to glargine+lispro.
The PARADIGM study
Patients with type 2 diabetes (T2D) can fail to achieve optimal glycaemic control despite diet, exercise and oral anti-hyperglycaemic agents, however, long-term glycaemic control on insulin therapy reduces the risk of both micro and macrovascular complications. In these patients, basal-bolus insulin treatment may be more complicated than premixed insulin therapy due to more daily injections, different types of insulin and injection devices and more rigorous monitoring.
A randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, open-label study, compared a premixed insulin (75% insulin lispro protamine suspensión, 25% insulin lispro [Humalog Mix25]; n = 177) with one daily glargine injection and progressing up to three additional daily insulin lispro injections (glargine+lispro; n = 184) as needed to meet glycaemic targets. Patients aged 30-80 years with T2D, BMI < 35 kg/m2, and inadequate glycaemic control (HbA1c 7.0-11.0%) on oral anti-hyperglycaemic agents were included. The primary efficacy measure was change in HbA1c from baseline to 48 weeks. Safety was assessed with overall, nocturnal and severe hypoglycaemia rates.
Humalog® Mix25 treatment was found to be non-inferior to insulin glargin+lispro. Moreover, the least-squares mean change in HbA1c was significantly higher with Humalog® Mix25 than with glargine+lispro.
The PARADIGM study showed that Humalog Mix 25 is a convenient option for patients with T2D who failed to oral agents because, when initiating and intensifying insulin treatment, they achieved optimal glycaemic control, associated with lower body weight increase compared to standard therapy, without increasing the apperance of hypoglycaemic events.