Results of ELLIPSE trial are of major significance as they show that Victoza addition to Metformin helps in further reduction of A1c and fasting plasma glucose. The efficacy and safety appear to be similar as in adults. The most common side effects are gastrointestinal in nature. Based on ELLIPSE trial outcomes, I anticipate broadening of FDA indications for Victoza, to include children and adolescents
GT
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N E J M
ELLIPSE
April 2019
BACKGROUND
Metformin is the regulatory-approved treatment of choice for most youth with type 2 diabetes early in the disease. However, early decreased glycemic control has been observed with metformin monotherapy. Whether liraglutide added to metformin (with or without basal insulin treatment) is safe and effective in youth with type 2 diabetes is unknown.
METHODS
Patients 10-17 years of age were randomly assigned, in a 1:1 ratio, to receive subcutaneous liraglutide up to 1.8 mg per day or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period.
Inclusion criteria were:
- The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group.
- The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo)
- But the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.
CONCLUSIONS
In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events.
- The mean A1c had decreased by 0.64% with liraglutide and increased by 0.42% with placebo, for an estimated treatment difference of −1.06% (P<0.001)
- A1c difference increased to −1.30% by 52 weeks.
Secondary endpoints
- The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group.
- The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo)
- But the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.
CONCLUSIONS
In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events.
- Primary endpoint was the A1c change from baseline after 26 weeks.
- Secondary endpoints included the change in fasting plasma glucose level.
RESULTS
Of 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients).
Demographic characteristics were similar in the two groups (mean age, 14.6 years).
Primary efficacy endpoint at 26-weeks:
- The mean A1c had decreased by 0.64% with liraglutide and increased by 0.42% with placebo, for an estimated treatment difference of −1.06% (P<0.001)
- A1c difference increased to −1.30% by 52 weeks.
Secondary endpoints
- The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group.
- The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo)
- But the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.
CONCLUSIONS
In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events.
- BMI >85th percentile
- A1c = 7.0-11.0% if the patients were being treated with diet and exercise alone or
- A1c = 6.5-11.0% if they were being treated with metformin (with or without insulin).
All patients received metformin during the trial.
- Primary endpoint was the A1c change from baseline after 26 weeks.
- Secondary endpoints included the change in fasting plasma glucose level.
RESULTS
Of 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients).
Demographic characteristics were similar in the two groups (mean age, 14.6 years).
Primary efficacy endpoint at 26-weeks:
- The mean A1c had decreased by 0.64% with liraglutide and increased by 0.42% with placebo, for an estimated treatment difference of −1.06% (P<0.001)
- A1c difference increased to −1.30% by 52 weeks.
Secondary endpoints
- The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group.
- The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo)
- But the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.
CONCLUSIONS
In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events.