Liraglutide seems safe, effective in children already on metformin

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.