Sanofi has presented data from two studies demonstrating Lyxumia (lixisenatide), a once-daily investigational GLP-1 agonist, in combination with basal insulin plus oral anti-diabetic agents (OADs), significantly reduced HbA1c levels in people with type 2 diabetes who were either new to insulin therapy (as early as 12 weeks after initiation) or already treated with insulin (for an average of 3.1 years).
Both studies, GetGoal Duo 1 and GetGoal-L, achieved the primary efficacy endpoint of HbA1c improvement with an associated significant reduction in post-prandial glucose (PPG).
In the GetGoal Duo 1, randomized, double-blind, multicenter study, 898 insulin-naïve patients were treated with insulin glargine (Lantus), which was titrated to reach a target fasting plasma glucose (FPG) of 80-100 mg/dL for a 12-week run-in phase period.
After the run-in phase, 446 patients with HbA1c >7% (despite controlled FPG levels) received either once-daily lixisenatide 20 µg or placebo for 24 weeks while metformin and insulin glargine titration were continued.
During the run-in period, HbA1c decreased on average from 8.60% to 7.60% with use of insulin glargine. The addition of lixisenatide led to a further significant HbA1c decrease to a mean value of 6.96% after 24 weeks compared to 7.3% in patients receiving placebo. A significantly higher percentage of patients achieved target HbA1c <7.0% with lixisenatide compared to placebo (56.3% vs. 38.5%, respectively, p=0.0001).
Associated with HbA1c reduction, lixisenatide also significantly improved 2-hour PPG after a standardized breakfast.
Patients receiving lixisenatide had higher incidence of hypoglycemia (22.4%) compared to those receiving the placebo (13.5%). Increased cases of nausea and vomiting were also reported in the lixisenatide group.
In the GetGoal-L, a 24-week randomized, double-blind multicenter, placebo-controlled study, 495 people with insufficiently controlled type 2 diabetes while using basal insulin with or without metformin, who received lixisenatide, had a significant reduction in HbA1c levels compared to placebo. They also saw a significant decrease in mean 2-hour PPG after a standardized breakfast.
Patients in the group receiving lixisenatide also experienced a significant mean reduction in body weight compared to placebo. The incidence of per protocol symptomatic hypoglycemia was 27.7% for lixisenatide vs. 21.6% for placebo. Severe hypoglycemia occurred in 1.2% of patients treated with lixisenatide compared to none with placebo. Other common adverse events were nausea (26.2%), vomiting (8.2%), and diarrhea (7.3%).
The European Medicines Agency (EMA) acknowledged receipt of the Marketing Authorization Application filing for Lyxumia (lixisenatide) in November 2011. Submission for regulatory approval of lixisenatide in the U.S. is expected in Q4 2012. The proprietary name for lixisenatide in the United States is under consideration.