Sanofi has announced data demonstrating Lyxumia ( Lixisenatide ), a once-daily investigational GLP-1 agonist, in combination with basal Insulin plus oral anti-diabetic agents, significantly reduced HbA1c ( glycated hemoglobin ) 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 GetGoal Duo 1 and GetGoal-L studies achieved the primary efficacy endpoint of HbA1c improvement with an associated significant reduction in post-prandial glucose.

Efficacy and safety of once-daily Lixisenatide added on to titrated Glargine plus oral agents in type 2 diabetes: GetGoal Duo 1 study

GetGoal Duo 1 is a randomized, double-blind, multicenter study, assessing the efficacy and safety of Lixisenatide, compared to placebo, in combination with Insulin glargine and oral anti-diabetic agents, ( mostly Metformin ).

During the 12-week run-in phase, 898 insulin-naïve patients were treated with Insulin glargine, which was titrated to reach a target fasting plasma glucose ( FPG ) of 80-100 mg/dL.
After the run-in phase, 446 patients with HbA1c less than 7% ( despite controlled FPG levels ) received either once-daily Lixisenatide 20 microg or placebo for 24 weeks while Metformin and Insulin glargine titration were continued.

HbA1c decreased on average from 8.60% to 7.60% during the run-in period with 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 ( p<0.0001 ).
A significantly higher percentage of patients achieved target HbA1c less than 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 post-prandial glucose, after a standardized breakfast, with a mean difference of -3.16 mmol/L ( p<0.0001 ) compared to placebo.

The mean difference in change in body weight between the Lixisenatide and placebo groups was -0.89 kg ( p=0.0012 ).

Incidence of symptomatic hypoglycemia was 22.4% among patients receiving Lixisenatide vs 13.5% in the placebo group. Other common adverse events in the Lixisenatide group were nausea and vomiting, which occurred in 27.4% and 4.9%, respectively, compared to placebo ( 9.4% and 1.3%, respectively ). Eighty-eight percent of patients in the Lixisenatide arm reached and remained on the 20 microg maintenance dose.

Efficacy and safety of once-daily Lixisenatide in type 2 diabetes insufficiently controlled with basal Insulin ± Metformin: GetGoal-L study

Also announced at the American Diabetes Association 72nd congress were data from GetGoal-L, a 24-week randomized, double-blind multicenter, placebo-controlled study of 495 people with type 2 diabetes, insufficiently controlled on basal Insulin with or without Metformin.

In the Lixisenatide arm, mean HbA1c was significantly reduced from baseline compared to placebo ( -0.74% vs -0.38%, p=0.0002 ) along with a significant decrease in mean 2-hour post-prandial glucose ( -5.54 mmol/L vs -1.72 mmol/L, p<0.0001 ), after a standardized breakfast.

Patients in the Lixisenatide arm of the study also experienced a significant mean reduction in body weight compared to placebo ( -1.8 kg vs -0.52 kg, p<0.0001 ).

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% ).

Source: Sanofi, 2012

XagenaMedicine2012