Liraglutide improves glycaemic control in adolescents with T2D
A 26-week regimen of liraglutide effectively improved glycaemic control in adolescents with type 2 diabetes (T2D) who had inadequate response to metformin, according to the results of the phase III Ellipse* trial presented as a poster at the recent Pediatric Academic Societies meeting (PAS 2019).
In this multinational study, 135 patients aged 10 to <17 years (mean age 14.6 years, 61.9 percent female, mean BMI 33.9 kg/m2) with T2D (HbA1c 7.0–11.0 percent [or 6.5–11.0 percent if already receiving metformin ± insulin]) were randomized 1:1 to receive subcutaneous liraglutide (≤1.8 mg/day escalated over 2–3 weeks from a starting dose of 0.6 mg/day) or placebo for 26 weeks (double-blind phase) in addition to metformin with or without insulin. This was followed by a 26-week open-label phase where patients randomized to liraglutide continued to receive the drug, while those randomized to placebo received metformin with or without insulin. All patients also followed a diet and exercise regimen.
At 26 weeks, patients who received liraglutide experienced a reduction from baseline in mean HbA1c levels compared with placebo recipients whose mean HbA1c levels increased (-0.64 vs 0.42 percentage points, estimated treatment difference [ETD], -1.06 percentage points, 95 percent confidence interval [CI], -1.65 to -0.46; p<0.001). [PAS 2019, publication number 2871.617; N Engl J Med 2019;doi:10.1056/NEJMoa1903882]
By week 52, the ETD between the two groups was -1.30 percentage points (95 percent CI, -1.89 to -0.70), with a 0.50 percentage point reduction in mean HbA1c levels among liraglutide recipients compared with a 0.80 percentage point increase in those randomized to placebo.
A greater proportion of liraglutide than placebo recipients achieved HbA1c <7.0 percent (63.7 percent vs 36.5 percent; p<0.001).
Liraglutide recipients also experienced a reduction in mean fasting plasma glucose levels at 26 weeks compared with placebo recipients whose levels increased (-1.08 vs 0.80 mmol/L, ETD, -1.88 mmol/L, 95 percent CI, -3.09 to -0.66; p<0.002).
While patients in both groups experienced reductions in mean body weight at 26 weeks (-2.3 vs -0.99 kg for liraglutide and placebo recipients, respectively), only liraglutide recipients maintained weight loss at 52 weeks (-1.91 vs 0.87 kg).
A similar number of liraglutide and placebo recipients experienced adverse events (AEs; n=56 vs 55), though the AE rate per 1 patient-year of exposure was higher with liraglutide than placebo (7.144 vs 5.425), which was mostly driven by an elevated incidence of gastrointestinal events among liraglutide recipients. Nausea, vomiting, and diarrhoea were the most common AEs among liraglutide recipients (28.8, 25.8, and 22.7 percent, respectively), while nasopharyngitis, headache, and diarrhoea were the most common among placebo recipients (27.9, 19.1, and 16.2 percent, respectively). Serious AEs were more common among liraglutide than placebo recipients (13.6 percent vs 5.9 percent), as was the incidence of minor hypoglycaemia (24.2 percent vs 10.3 percent).
The low number of patients who received the maximum liraglutide dose (55.6 percent) may have impacted the findings, particularly the safety findings, and may also explain the lack of difference with placebo recipients in terms of BMI at week 26, said the researchers.
“We’ve not been able to get drugs approved for children beyond metformin and insulin [and] we urgently need other options for medical treatment of T2D in our youth under age 18,” said study co-author Professor Jane Lynch from the University of Texas Health Science Center, San Antonio, Texas, US.
“This adult diabetes medication was very effective in our trial of youth with T2D and was well tolerated. If approved, this drug would be a fantastic new option to complement oral metformin therapy as an alternative to insulin for our youth and adolescents with T2D,” she said.