BOSTON — Achieving greater reductions in HbA1c with fixed-ratio combination insulin glargine/lixisenatide (LixiLan) did not increase rates of hypoglycemia when compared with insulin glargine alone in patients with type 2 diabetes on metformin, researchers reported at the American Diabetes Association (ADA) 75th Scientific Sessions.
“Approximately 50% to 60% of patients with type 2 diabetes can achieve glycemic targets using titrated basal insulin mainly by controlling nocturnal and fasting plasma glucose levels,” Julio Rosenstock, MD, of the Dallas Diabetes and Endocrine Center in Texas, said during a presentation of the data.
“Prandial GLP-1 receptor agonists with a predominant post-prandial glucose effect can have a more predictable complementary action to tailor the combination with basal insulin therapy and are not associated with adverse effects on body weight and hypoglycemia.”
Therefore, Rosenstock and colleagues conducted a 24-week proof-of-concept study to see if it were possible to improve glucose control without increasing hypoglycemia risk at any level of HbA1c reduction by adding LixiLan to metformin in patients with type 2 diabetes.
A total of 323 insulin-naïve patients (mean age, 56.7 years; mean diabetes duration, 6.7 years) with a mean baseline HbA1c of 8.0% were included in the study. Patients were randomly assigned to metformin plus insulin glargine alone (n=162) or metformin plus LixiLan (n=161).
Results showed that titrated LixiLan added on to metformin improved HbA1c from 8.1% at baseline to 6.3% while 84% also achieved an HbA1c lower than 7.0%. Further, 68% achieved an HbA1c lower than 7.0% with no documented hypoglycemia, 56% achieved an HbA1c lower than 7.0% with no weight gain and 46% achieved an HbA1c lower than 7.0% with no weight gain and no documented hypoglycemia.
Nausea and vomiting with LixiLan were also less frequent than what has been reported for the GLP-1 receptor agonist class.
In a post-hoc analysis, the researchers sought to determine whether a correlation exists between the HbA1c reduction observed with LixiLan and rates of hypoglycemia.
They looked at hypoglycemia rates in subgroups based on different HbA1c levels. Symptomatic hypoglycemia was defined as an event with typical symptoms of hypoglycemia and was documented by a measured plasma glucose concentration of 70 mg/dL or less.
The researchers categorized patients based on achieving HbA1c levels of less than 6%, 6% to less than 6.5%, 6.5% to less than 7% and 7% or higher. They also evaluated patients according to absolute mean reduction in HbA1c from baseline to 24 weeks, including 1% or less, greater than 1% to 1.5%, greater than 1.5% to 2% and greater than 2%.
Results revealed no statistically significant relationship between hypoglycemia rates and HbA1c levels reached at week 24 or absolute mean reduction in HbA1c from baseline (P>.1).
“Reaching lower near-normal HbA1c levels and achieving greater HbA1c reductions with LixiLan vs. insulin glargine alone did not increase rates of hypoglycemia at any level of glucose control,” Rosenstock concluded.
- Rosenstock J et al. Abstract 169-OR: Improved Glucose Control without Increased Hypoglycemia Risk at Any Level of HbA1c Reduction with Insulin Glargine/Lixisenatide Fixed-Ratio Combination (LixiLan) vs. Insulin Glargine Alone Both Added On to Metformin in Type 2 Diabetes (T2DM). Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.