A recent study showed that the drug golimumab was able to result in better endogenous insulin production and less use of exogenous insulin in patients with type 1 diabetes.
The research, published in the New England Journal of Medicine, included newly diagnosed children and young adults with diabetes.
Type 1 diabetes and Golimumab
Type 1 diabetes is a form of disease in which insulin produced by the islets of Langerhans, in the pancreas, is very little or even absent. The most frequent symptoms are increased thirst, frequent urination, and weight loss.
Relatively rapid onset complications include diabetic ketoacidosis and non-ketotic hyperosmolar coma. Long-term complications include the most common cardiovascular diseases, such as myocardial infarction and stroke, kidney failure, ulcerative foot lesions and a specific form of retinopathy.
The cause of type 1 diabetes is unknown, but it is believed to be due to a combination of genetic and environmental factors. The final result is a destruction of pancreatic beta cells by autoimmune mechanisms.
Golimumab is a human monoclonal antibody that is used as an immunosuppressive drug and works by inhibiting tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory molecule.
On the other hand, TNF-alpha is a cytokine that appears to play a role in different autoimmune diseases and exert toxic effects on pancreatic beta cells.
Studies conducted on animal models have shown that TNF-alpha is capable of inducing the development of autoimmune diabetes. In addition, elevated serum levels of TNF-alpha have been shown in patients with type 1 diabetes.
To date, Golimumab is approved for use in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis. It is administered by subcutaneous or intravenous injection.
A phase 2 multicenter trial
In this new study, the researchers investigated whether golimumab treatment was able to preserve beta cell function and improve key diabetes-related clinical and metabolic parameters in newly diagnosed children and young adults with type 1 diabetes.
In a double-blind, controlled design, this multi-center phase 2 trial randomized children and young adults to subcutaneous golimumab or placebo for 52 weeks in a 2: 1 ratio.
The primary endpoint of the study 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 at week 52.
Secondary and additional endpoints included insulin use, glycated hemoglobin level, number of hypoglycemic events, ratio of fasting proinsulin to C-peptide over time, and response profile.
Overall, of the 84 randomized participants, 56 were assigned to the golimumab group and 28 to the placebo group.
The C peptide levels at 4 hours
At week 52, C-peptide levels at 4 hours differed significantly between the golimumab group and the placebo group (0.64 pmol per milliliter versus 0.43 pmol per milliliter, P <0.001). In both groups, the treatments led to good glycemic control, but insulin use was lower with golimumab than with placebo.
Partial remission was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group.
Regarding treatment safety, the mean number of hypoglycemic events was similar in the two study groups, but hypoglycemic events recorded as adverse events, at the investigator’s discretion, occurred in 23% of the subjects under active treatment and in 7% of those treated with placebo. Antibodies to golimumab were detected in 30 participants who received the drug.
Effective and well tolerated drugs
Although we are in the initial stages of evaluation of this new molecule, and not many patients were included in this new trial, this study has shown a substantial therapeutic effect of golimumab in the treatment of type 1 diabetes.
While considering that the aspects related to the safety of the treatment will certainly need to be investigated, this innovative drug could be proposed not only as an effective treatment for glycemic control, but also as a therapy capable of arresting the progression of the disease at the level of pancreatic beta cells.
Considering that type 1 diabetes afflicts more than 13 million people worldwide, and that its incidence is constantly increasing at a rate of 3-4% per year, having effective and well tolerated drugs is extremely important to reduce the burden of this disease.
This post is also available in: Chinese (Simplified)