Groundbreaking finding- Verapamil an effective therapy for Type 1 diabetes

A new study published in the journal Nature Medicine shows the drug, verapamil, targets diabetes by promoting the functioning of the insulin-producing beta cell in the patient, enabling the body to produce its own insulin. This is an effective and safe novel therapy limiting the hypoglycemic episodes and insulin requirements of patients with recent onset Type 1 diabetes.

The study, which is first such discovery to target diabetes in this manner identifies verapamil as a safe, effective, and promising therapy -- a groundbreaking finding in the field of diabetes research.

Fernando Ovalle, researcher, Comprehensive Diabetes Center, the University of Alabama at Birmingham, and colleagues conducted the randomized double-blind placebo-controlled phase 2 clinical trial to determine whether verapamil causes diabetes reversal in humans, as in mouse models.

Type 1 diabetes (T1D) occurs as the result of one's immune system attacking the beta cells in the pancreas that produce insulin to regulate and maintain optimal blood sugar levels. When beta cells are being destroyed, a person's ability to produce insulin declines, causing blood sugar levels to rise and making the person more and more dependent on external insulin.

The findings reveal that regular oral administration of verapamil, a common blood pressure medication first approved for medical use in 1981, enabled patients to produce higher levels of their own insulin, limiting their need for insulin injections to balance out their blood sugar levels.

"The data collected from our clinical trial gives us every indication to believe that individuals with Type 1 diabetes have the promise of a treatment approach that would reduce their external insulin requirements and improve their blood sugar control and quality of life, thanks to the effects that verapamil has in promoting the body's own beta cell function," said Anath Shalev, M.D., director of UAB's Comprehensive Diabetes Center and principal investigator of the trial. "While this research is not an end-all cure for Type 1 diabetes, these findings are getting us closer to disease-altering therapies that can enable individuals with Type 1 diabetes to have more control over their disease and maintain some of their body's own insulin production."

In 2014, Shalev's UAB research lab discovered that verapamil completely reversed T1D in animal models and sought to test the effects of the drug in human subjects in a clinical trial.

"At JDRF, we are excited and encouraged by the recent findings from the UAB Comprehensive Diabetes Center's clinical trial. This data has the potential to change how we think about treating and ultimately curing T1D," explains Andrew Rakeman, Ph.D., assistant vice president of research at JDRF. "We look forward to continued clinical studies that will build on and confirm these findings, expanding to additional patient populations and guiding how, when and in who verapamil might have the most impact in T1D."

The verapamil clinical trial monitored 24 patients age 18 to 45, each over the course of one year. Eleven patients received verapamil and 13 received placebo. All clinical trial participants were diagnosed with T1D within three months of their start in the trial and continued with their prescribed insulin pump therapy throughout the duration of the study. Researchers monitored the placebo and verapamil groups' total daily dose of insulin, the amount of insulin produced, the percent change in insulin production, and their HbA1C levels. In addition, the number of hypoglycemic events that the patients experienced were recorded, and the percent of time each patient registered in healthy blood glucose ranges were analyzed using a continuous glucose monitoring system.

"Although this is a smaller sample group, our trial results give us promise that subjects with Type 1 diabetes have therapy options and that we are nearing a more effective way to deal with this disease," said Fernando Ovalle, M.D., director of UAB's Comprehensive Diabetes Clinic and co-principal investigator of the study. "Beyond verapamil allowing subjects with Type 1 diabetes the ability to live a life with less external insulin dependence, these findings will impact the quality of life that they can have. Hopefully, by improving overall blood sugar control it will also limit their risks for other comorbidities, including heart attack, blindness, kidney disease, and more."

While this study specifically addressed findings in adult subjects diagnosed within three months of the trial's start, Shalev notes that future long-term studies are needed to help determine the effect of verapamil on both the pediatric T1D population, and individuals with T1D who have been living with and/or diagnosed with the disease longer than three months. Furthermore, verapamil's effects on Type 2 diabetes have not been tested or studied in prospective controlled trials; Shalev said and future studies that explore the potential for this regimen to positively impact Type 2 diabetes are therefore also needed. However, in mouse models of Type 2 diabetes and in recent epidemiological studies verapamil use has been associated with lower risk of developing Type 2 diabetes and with better blood sugar control.

For further information log on to http://dx.doi.org/10.1038/s41591-018-0089-4