An Effective Treatment for Type 1 Using a Blood Pressure Medication

Verapamil might serve as a potential breakthrough allowing type 1 diabetes patients to produce their insulin. 

Type 1 diabetes affects a tiny section of the diabetes population and can be referred to as an autoimmune disease caused by the absolute destruction of the pancreatic cells. Therefore, type 1 diabetes patients are dependent on daily insulin hormone replacement for survival. Before this study, previous research by Dr. Shalev and colleagues had shown that verapamil completely reverses diabetes in mice by lowering levels of the protein called TXNIP in beta cells. 

This study was conducted to prove the effectiveness of the previous studies in humans and to provide clinical insight into the therapeutic effect of verapamil in newly diagnosed type 1 diabetes patients using proteomics analysis and RNA sequencing. The study was a double-blinded, controlled, randomized placebo trial based on a well-known blood pressure medication, Verapamil, that has been in the market for 30 years. Verapamil is a calcium channel blocker used to treat hypertension and migraine. The trial eligibility includes patients aged 19-45 years with a recent diagnosis of type 1 diabetes within the last three months. During the trial, patients were randomized to receive either 360mg sustained released verapamil or placebo daily for one year while using their insulin injection or pump. In addition, patients were given the option to choose either on or off verapamil in the second year of the trial. This resulted in five people receiving verapamil for two years, four subjects discontinuing active study treatment for the second year, and six participants allocated to the control group receiving no active study drug for the two years. During the trial, patients were monitored for blood sugar control and their ability to produce insulin. The researchers also used peptide response to the mixed meal to measure the patient’s functional beta cell mass indirectly. Statistical analysis of the study was conducted using a linear regression model to analyze the effect of the treatment.  

The study’s global type 1 diabetes (T1D) serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the most altered protein by verapamil and as a potential therapeutic marker, revealing that verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. The researchers employed liquid chromatography-tandem mass spectrometry of blood serum samples from participants diagnosed with type 1 diabetes within three months of diagnosis and at one year of follow-up to look at changes in circulating proteins in response to verapamil medication. The blood protein chromogranin A, or CHGA, was the most affected by verapamil therapy, as it was downregulated. In reaction to verapamil, 53 proteins demonstrated a significant change in relative abundance over time(p<0.05). These included proteins linked to immune regulation and type 1 diabetes autoimmunity. CHGA levels were also readily detected in serum after blood draw using a simple ELISA technique. Serum CHGA levels in healthy, non-diabetic volunteers were nearly twofold lower than those in type 1 diabetes patients. After one year of verapamil treatment, CHGA levels in type 1 diabetes patients were comparable to those in healthy people.

This study is interesting because it poses a potential breakthrough to the diabetes population and its treatment. In a one-year clinical investigation of type 1 diabetes patients, the researchers discovered that frequent oral administration of verapamil helped patients create higher quantities of their insulin, reducing their requirement for injectable insulin to control blood sugar levels. Furthermore, the study findings imply that long-term administration of oral verapamil in type 1 diabetes patients may delay beta-cell loss and minimize insulin requirements for at least two years after diagnosis; also, changes in serum chromogranin A (CHGA) can be an indication of therapeutic effectiveness or disease progression.

They also discovered that verapamil modulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic, and immunomodulatory gene expression profile in human islets, implying that these protective modifications, taken together, could explain the overall positive benefits of verapamil. 

Practice Pearls:

• Diabetes is becoming a more widespread chronic worldwide health issue that affects people of all ages.
• This study analyses RNA sequencing and provides clinical insights into the therapeutic effects of verapamil in newly diagnosed type 1 diabetes patients.
• This study shows that continuous oral verapamil in type 1 diabetes may slow disease progression.

Xu G, Grimes TD, Grayson TB, et al. Exploratory study reveals far-reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes. Nature Communications. 2022;13(1). doi:10.1038/s41467-022-28826-3

Betsy Adegborioye, PharmD Candidate 2022, South College School of Pharmacy