First Human Data Show Verapamil Lowers Glucose in Diabetes

Marlene Busko

February 29, 2016

In the first study to examine whether the calcium-channel blocker verapamil lowers glucose in humans (as it does in mice), this old drug that has long been used to treat hypertension, cardiac arrhythmia, and migraine was indeed associated with a lower fasting serum glucose in diabetic patients.

The observational study of a subset of close to 5000 patients who had diabetes and were participating in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, by Dr Yulia Khodneva, from the University of Alabama at Birmingham (UAB), and colleagues, was published online February 12 in Diabetes Research and Clinical Practice.

Among these patients who had type 1 diabetes or late-stage type 2 diabetes (ie, were taking insulin or insulin plus an oral antidiabetic agent), those who also received verapamil had fasting serum glucose levels that were 24 mg/dL lower than their peers who were not receiving verapamil (P = .039).

This 24-mg/dL difference in fasting serum glucose is "dramatic," since it is roughly equal to an HbA1c drop from 8% to 7% (where 7% is the American Diabetes Association treatment target), Dr Khodneva told Medscape Medical News.

However, the current study is observational and very preliminary, she stressed.

More answers should be forthcoming about 18 months from now when results start to emerge from "the repurposing of verapamil as a beta-cell survival therapy in type 1 diabetes" randomized controlled trial that fellow researchers at UAB are conducting.

That study has so far enrolled 20 adults aged 18 to 45 with recent-onset type 1 diabetes (of a planned enrollment of 52 such patients), to see whether 12 months of daily oral verapamil will improve insulin production.

"I think that if this is a positive trial, it will be widely published," and it's probably going to affect clinical practice right away, Dr Khodneva speculated.

A New Strategy to Delay Beta-Cell Death?

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Source: UAB News

This new line of research began after investigators at UAB observed that in type 1 diabetes, the pancreatic beta cells have an increased concentration of intracellular calcium, and a substance called thioredoxin-interacting protein (TXNIP) is overexpressed, which induces beta-cell apoptosis.

They further identified that calcium-channel blockers, especially verapamil, decreased TXNIP expression in a mouse model and in human pancreatic beta cells. Verapamil also reversed diabetes in mice that had streptozotocin-induced diabetes.

"These emerging findings raise the intriguing possibility that a familiar widely used drug, verapamil, may have new indications if similar results can be found in humans," the researchers write.

The REGARDS study, designed to look at stroke risk, recruited more than 30,000 community-dwelling adults age 45 and older from every state in continental United States in 2003 to 2007 and was race and gender balanced, making it a valuable national data set for the current observational study.

Participants had fasting serum glucose measurements, other blood and urine tests, and a review of their medication bottles.

The researchers identified 22 calcium-channel blockers, including verapamil, and looked at how they were linked with fasting serum glucose levels among the 4978 adults with diagnosed diabetes.

The 1484 (29.6%) of diabetic patients in REGARDS who were taking a calcium-channel blocker had, on average, a 5-mg/dL lower serum blood glucose than the patients who were not taking a drug from this class, after adjustment for multiple potential confounders (including demographics and cardiovascular disease risk factors).

Moreover, the 174 (3.4%) of diabetic patients in REGARDS who were taking verapamil had an even more striking average 10-mg/dL lower blood glucose than patients who were not taking a calcium-channel blocker.

When confined to just those with diabetes on insulin and taking oral antidiabetic agents, the reduction was 24 mg/dL, and among diabetic patients who were taking insulin alone, those who were also taking verapamil had a dramatic, 37-mg/dL lower fasting serum glucose than those who did not receive verapamil (P = .06); the lack of statistical significance is likely explained by the small number of patients in this group (only 15), Dr Khodneva suggested.

If clinically meaningful findings are confirmed in other studies, this could have a big impact on treating two types of patients: those with advanced type 2 diabetes and those with new-onset type 1 diabetes.

This "could usher in a new therapeutic option for glycemic control in a particularly challenging subset of type 2 diabetes patients" who are dependent on insulin and have a hard time achieving glycemic control, the researchers write. In addition, "verapamil may be an exciting new strategy for delaying beta-cell death in type 1 diabetes."

Dr Khodneva has no relevant financial relationships. Disclosures for the coauthors are listed in the article.

Diabetes Res Clin Pract. Published online February 12, 2016. Abstract

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