Use of metformin with or without liraglutide results in improved glycaemia but falls short of suppressing the high rates of gluconeogenesis in patients with youth-onset type 2 diabetes (Y-T2D), reports a study.
Twenty-two children with Y-T2D (mean age 15.3 years, 68 percent female, body mass index [BMI] 40.1 kg/m2, duration of diagnosis 1.8 years) were randomly assigned to receive metformin alone or metformin plus liraglutide. Participants were assessed before and after 12 weeks of treatment.
The researchers measured gluconeogenesis (2H2O) and glucose production (6,6-2H2) glucose after an overnight fast and during a continuous meal using stable isotope tracers. They also assessed β-cell function (sigma) and whole-body insulin sensitivity (mSI) during a frequently sampled 2-h oral glucose tolerance test.
Gluconeogenesis, glucose production, and fasting and 2-h glucose were similar between the two treatment groups at baseline, but patients in the metformin plus liraglutide arm had higher haemoglobin A1C levels. The combination therapy group showed a greater reduction in fasting glucose (‒2.0 vs ‒0.6 mmol/L; p=0.008) and a greater increase in sigma (0.72 vs ‒0.05; p=0.03) from baseline.
The change in fractional gluconeogenesis did not differ significantly between the two treatment groups (combination vs monotherapy: ‒0.36 percent vs 0.04 percent; p=0.9). On the other hand, no changes were seen in prandial gluconeogenesis or mSI. Moreover, the increased glucose clearance in both arms was related to sigma (r, 0.63; p=0.003) but not gluconeogenesis or mSI.
“Novel therapies that will enhance β-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed,” the researchers said.