Potential benefits of ribavirin and pleconaril treatment on type 1 diabetes


Type 1 diabetes (T1D) is caused by the progressive decline of pancreatic beta cell functions, leading to lifelong insulin dependence. Despite extensive immunological, biochemical, clinical, and epidemiological research, T1D etiology remains unclear.

Previous studies have shown that viral infections can result in the pancreas becoming autoimmune and leading to diabetes. In particular, enteroviral infections may contribute to T1D pathogenesis.

In a recent study published in the journal naturopathyResearchers are investigating whether ribavirin and pleconaril administration can stimulate endogenous insulin production in individuals with type 1 diabetes (T1D).

Study: Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial.  Image Credit: VGStockStudio / Shutterstock.com Study: Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial. Image Credit: VGStockStudio / Shutterstock.com

about the study

The Diabetes Virus Detection (DiViD) placebo-controlled, parallel-group, double-blind randomized control trial (RCT) was conducted at the Steno Diabetes Center Copenhagen/Harlev University Hospital in Denmark and Oslo University Hospital in Norway. The RCT involved 96 individuals aged six to 15 with T1D, who were divided into an intervention group and a placebo group.

The intervention group consisted of 47 individuals, of which 28 were men and 19 were women, who received oral antiviral therapy with ribavirin at a dose of 7.5 mg/kg twice a day and pleconaril at a dose of five mg/kg twice a day for six months. Preserve pancreatic beta cell function.

The placebo group consisted of 49 individuals, 28 men and 21 women, who received placebo treatment. The screening period lasted three weeks from T1D diagnosis until study initiation. All study participants were followed up continuously for 26 weeks for two years.

The primary study endpoint was endogenous secretion of insulin, assessed using the average two-hour serological C-peptide area under the receiver-operating characteristic curve (AUC) values ​​during a mixed-meal tolerance test (MMTT) after one year of treatment. Was done by. , Linear mixed modeling was performed to determine the average marginal effect (AME) for the endpoint.

Longitudinal log-transformed serological C-peptide AUCs were also determined at study initiation, three months, six months, and one year. Secondary study endpoints included peak serological C-peptide values ​​greater than 0.20 picomoles (pmol)/mL, glycated albumin, insulin dose, glycated hemoglobin (HbA1c), and hypoglycemic events such as seizures and syncope during the MMTT.

MMTT tests were performed in hospitals in the early morning under fasting conditions, with blood samples obtained at 15, 30, 60, 90, and 120 minutes after consumption of a standard liquid meal. Liquid chromatography with tandem mass spectrometry (LC-MS) was performed to determine glycated albumin levels.

Enteroviruses were detected using reverse transcription-polymerase chain reaction (RT-PCR) assay in nasopharyngeal aspirates, nasal swabs, saliva samples, stool samples, and serological samples.

Individuals diagnosed with stage three T1D using American Diabetes Association criteria and International Classification of Diseases, Tenth Revision (ICD-10) codes were recruited from August 20, 2018 to October 20, 2020.

The team excluded individuals treated with injectable or oral non-insulin antidiabetic drugs, suffering from hemolytic anemia or displaying significant hematological changes at screening, suffering from severe cardiovascular disease in the past six months, and those with renal impairment. In addition, individuals who had participated in other clinical studies in the past three months, pregnant or breastfeeding women, sexually active individuals who were not willing to use efficient contraceptives, and those with serious medical conditions People with were kept out.

study findings

The primary study endpoint was achieved, with serological C-peptide AUC values ​​higher among antiviral treatment recipients than placebo recipients at one year. Antiviral treatment was well tolerated among study participants.

At the beginning of the study, the average non-log-transformed two-hour C-peptide area under the curve values ​​in the intervention and placebo groups were 0.6 and 0.5 pmol/ml, respectively. After one year, the corresponding values ​​were 0.6 and 0.4 pmol/ml, respectively. At one year, the relative reduction in serological C-peptide AUC values ​​was 11% among therapy recipients and 24% among placebo recipients.

Approximately 86% of antiviral treatment recipients and 67% of placebo recipients demonstrated C-peptide levels above baseline, with a hazard ratio of 1.3. HbA1c values ​​in the intervention and placebo groups were 48 and 51 mmol/mol, respectively.

Individuals receiving antiviral treatment had significantly lower HbA1c values ​​at three and six months. Glycated albumin levels were slightly reduced in the intervention group after three and six months of therapy.

Insulin dose-adjusted glycated hemoglobin (IDAA1c) values ​​were comparable in both study groups at one year. However, at three and six months, IDAA1c values ​​were lower among antiviral treatment recipients compared to placebo recipients. The daily dose of insulin was the same in both groups during follow-up.

Severe hypoglycemic episodes were observed in two placebo recipients but no antiviral treatment recipients in the initial follow-up year. Adverse event rates in the initial year were 94% and 96% in the intervention and placebo groups, respectively.

No serious adverse events were reported in either group. Two antiviral therapy recipients developed mild to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection after three and five months of treatment; However, this was not reported in any placebo recipients.

conclusion

Based on study findings, ribavirin and pleconaril combination antiviral therapy may help maintain residual endogenous insulin secretion among young T1D patients. The study findings provide a rationale for further research to evaluate the effectiveness of antiviral agents in the prevention and treatment of T1D.

Journal Reference:

  • Krogvold, L., Mynarek, I.M., Ponzi, E., and others. (2023). Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial. naturopathy, doi:10.1038/s41591-023-02576-1

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