Golimumab Use in Type 1 Diabetes

According to research presented by Dr. Teressa Quattrin at the Jacobs School of Medicine and Biomedical Sciences, treatment with golimumab resulted in better endogenous insulin production in patients with type 1 diabetes.

Type 1 diabetes is an autoimmune disease characterized by the progressive loss of pancreatic beta cells to make insulin. This process can continue slowly before symptoms begin to appear. These symptoms include nausea, vomiting, thirst, and fatigue. Type 1 diabetes is usually diagnosed earlier in life and is less common than type 2, affecting 5 to 10% of those with diabetes. Around the world, 13 million people have type 1 diabetes, and the number is increasing each year steadily. Although there have been advances in technology and medicine, there is still a need for treatment that slows beta-cell loss.

This trial sought to determine whether treatment with golimumab would preserve the function of beta cells and improve diabetic measures in both children and young adults with type 1 diabetes. Dr. Quattrin and her colleagues submitted this research to the New England Journal of Medicine to examine and summarize the benefits of golimumab in this patient population. Golimumab is a human monoclonal antibody that is currently approved to treat various autoimmune diseases such as arthritis, colitis, and spondylarthritis. It is highly specific for tumor necrosis factor a (TNF-a). TNF-a is a proinflammatory cytokine that is linked to the progression of various autoimmune disorders. It is toxic to pancreatic beta cells. By controlling this, the beta cells have a better environment for producing insulin. In this trial, the authors used a multicenter, randomized, placebo-controlled, double-blind approach. A total of 108 patients were screened, and 84 were randomized to receive golimumab in a 2:1 ratio. Fifty-six patients were included in the treatment group, while 28 were in the control group. According to the American Disease Association, eligible patients were between the ages of 6 and 21 had a diagnosis of type 1 diabetes, peak C-peptide levels of at least 0.2, and positive antibody results. C-peptide levels were assessed using immunoassays and radioimmunoassay kits. All patients agreed to recommended immunizations, and patients with other significant diseases and autoimmune diseases were excluded. The primary endpoint was the production of endogenous insulin based on C-peptide levels. The secondary endpoints were the changes from baseline to finish of insulin, glycated hemoglobin, and the number of hypoglycemic events.

The results from this study showed that patients with type 1 diabetes who received golimumab resulted in better endogenous insulin production and less exogenous production. Patients in the treatment group had better glycemic control as well as used less insulin therapy. Additionally, 41% of patients in the treatment group had an increase in C-peptide levels. However, glycemic control in both groups had better reports than patients with type 1 diabetes in the general population. Lastly, hypoglycemic events described as adverse events were reported in 13 participants in the golimumab group and two patients in the placebo group.

In conclusion, the role of TNF-a in patients with type 1 diabetes has not been thoroughly examined. This trial was consistent with a previous trial using another TNF-a drug, etanercept. Both trials showed that when the C-peptide levels are increased, then the insulin use is decreased. As stated by Dr. Quattrin, initiating the medication golimumab could contribute to better endogenous insulin production for patients newly diagnosed with type 1 diabetes. Limitations of this study include using a small sample size. Another limitation includes determining how continuous glucose monitoring contributed to these results. The continuous monitoring could have led to better glycemic control compared to patients not being continuously monitored in clinical practice. The final limitation is that the trial had a limited number of participants with other coexisting conditions that were included. These factors may limit the application of these results in some settings.

Practice pearls

• Type 1 diabetes is an autoimmune disease characterized by the progressive loss of pancreatic beta cells used to make insulin.
• This trial sought to determine whether treatment with golimumab would preserve the function of beta cells and improve diabetic measures in both children and young adults with type 1 diabetes.
• The results from this study showed that patients with type 1 diabetes who received golimumab resulted in better endogenous insulin production and less exogenous production.

References

Quattrin, Teresa, et al. “Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes.” New England Journal of Medicine, vol. 383, no. 21, 2020, pp. 2007–2017., link

“Type 1 Diabetes.” Centers Disease Control and Prevention, Centers for Disease Control and Prevention, 25 Mar. 2021, link. 

“Type 1 Overview.” Type 1 Diabetes – Symptoms, Causes, Treatment, link

Kmeone Kingdom, MPH, PharmD Candidate, South College School of Pharmacy