Golimumab improves insulin production and blood sugar control in T1D: NEJM
Delhi: Golimumab results in better endogenous insulin production in children and young adults with newly diagnosed overt (stage 3) type 1 diabetes, suggests a recent study in the New England Journal of Medicine.
Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells that leads to lifelong dependence on insulin therapy. Golimumab is a human monoclonal antibody that is specific for tumor necrosis factor α -- already approved for the treatment of autoimmune conditions in adults and children. However it is unknown if golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes. To determine the same, the researchers conducted a phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial.
The trial included a total of 84 children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes. They were randomized in the ratio 2:1 to receive subcutaneous golimumab (n=56) or placebo (n=28) for 52 weeks.
The primary end point was endogenous insulin production, as assessed according to the area under the concentration–time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52.
Key findings of the study include:
- The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter).
- A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level.
- Insulin use was lower with golimumab than with placebo.
- A partial-remission response (defined as an insulin dose–adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group.
- The mean number of hypoglycemic events did not differ between the trial groups.
- Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 23% of patients in the golimumab group and in 7% of those in the placebo group.
- Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies.
"Our findings show that among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo," concluded the authors.
