Sanofi announced data from a 60-week, open-label study that compared three intensified insulin regimens added to oral therapy for uncontrolled type 2 diabetes and found that using two regimens including Lantus (insulin glargine [rDNA origin] injection) and Apidra (insulin glulisine [rDNA origin] injection) lowered blood glucose levels compared to premixed insulin with less hypoglycaemia and improvement in diabetes-specific quality of life.
“Optimization of insulin dosage with glargine plus a single mealtime injection of glulisine allowed more patients to reach target A1C levels than with twice-daily premixed insulin, and with less hypoglycaemia,” said Matthew Riddle, MD, head of the Oregon Health and Science University Section of Diabetes and lead investigator of one of the data analyses presented at the meeting. “These findings support a stepwise approach to addition of mealtime insulin when basal insulin with oral agents is not sufficient to maintain control.”
Three analyses of this data are being either presented or published at the American Diabetes Association’s 71st Scientific Sessions in San Diego, California.
The study was designed to evaluate glycemic control achieved by three intensified insulin regimens with two co-primary objectives: 1) to demonstrate superiority of Lantus plus up to 3 injections of mealtime Apidra versus premixed insulin, as measured by A1c<7% at week 60; and 2) to demonstrate non-inferiority of Lantus plus up to 1 injection of mealtime Apidra versus premixed insulin, based on the reduction from baseline to week 60.
Investigators compared the addition of twice-daily Novolog (insulin aspart) Mix 70/30 (PREMIX; n=192) versus Lantus plus up to one prandial dose of Apidra (GLARG + 0-1; n=189) versus Lantus with the stepwise addition of up to 3 injections of Apidra (GLARG+ 0-3; n=191) in 572 patients with type 2 diabetes who did not achieve glycemic control with oral therapy.
The patients enrolled in the study had a mean age of 54 years and body mass index of 33.2 kg/m2. They had been diagnosed with type 2 diabetes for an average of 9 years and were failing to control their diabetes despite two to three oral agents. The baseline A1C in this study was 9.4 per cent after a four-week run-in. Insulin was titrated seeking fasting and pre-prandial glucose <100 mg/dL in all treatment arms.
The study results supported the non-inferiority of Lantus plus up to 1 injection of Apidra versus two–injections of premixed insulin, while in the Lantus plus up to 3 injections of Apidra arm, superiority versus premixed insulin was not shown.
Based on the secondary endpoints, the combination of Lantus and Apidra led to significantly larger proportions of patients achieving target A1C with statistically lower rates of hypoglycaemia and significantly greater fasting plasma glucose reductions, although superiority versus premixed insulin was not achieved. The regimen consisting of a single dose of Apidra added to Lantus led to a greater decrease in HbA1c from baseline at week 60 (-2.30 per cent versus -1.97 per cent, p=0.036 NS), and a delayed and lesser need for insulin dose escalation compared to twice daily premixed insulin.
The percentage of patients who experienced treatment-emergent adverse events was similar across all treatment groups. The most common treatment-emergent adverse events (percentage of patients with events) by system, organ, class include: infections and infestations (upper respiratory infection, sinusitis, nasopharyngitis; 41.9%), musculoskeletal and connective tissue disorders (pain in extremity, back pain, musculoskeletal pain; 22.5%), nervous system disorders (hypoasthesia, dizziness, parasthesia; 17.0%) and gastrointestinal disorders (nausea, abdominal discomfort, dyspepsia; 16.8%).