A study comparing insulin lispro mix 25 with glargine plus lispro therapy in patients with Type 2 diabetes who have inadequate glycaemic control on oral anti-hyperglycaemic medication: results of the PARADIGM study

Diabet. Med. 29, e263-e272 (2012) Abstract Aims To test the hypothesis that initiation and intensification with 25% insulin lispro, 75% insulin lispro protamine suspension (LM25), is non-inferior to initiation and intensification with glargine + insulin lispro therapy on change from baseline in HbA1c. Methods In this randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, 48-week, open-label study, patients (n = 426) with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications were assigned to either initiating therapy with one daily LM25 injection, progressing up to three daily injections (full analysis set n = 211; per protocol set n = 177) or initiating therapy with one daily glargine injection and progressing up to three daily insulin lispro injections (full analysis set n = 212; per protocol set n = 184). Results LM25 therapy was found to be non-inferior to glargine + insulin lispro therapy by study end (upper limit of 95% CI < 0.4), with a least-squares mean difference (95% CI) in HbA1c (LM25 minus glargine + insulin lispro) of -0.4 mmol/mol (95% CI -2.7 to 1.9); -0.04% (95% CI -0.25 to 0.17). No statistically significant differences between treatment groups were found in the percentage of patients achieving HbA1c targets or postprandial blood glucose levels. The increase in insulin dose, number of injections and weight change during the course of the study were similar in both groups. Patients in both groups experienced similar hypoglycaemia rates and safety profile. Conclusions For patients with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications, glycaemic control when initiating and intensifying with LM25 therapy was found to be non-inferior to treatment with glargine + insulin lispro therapy.