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| Making a Life Saving Drug Even Better |
For intensive care patients, insulin therapy can be as fatal as it is vital, says Dariush Elahi, illustrating the relationship between blood glucose, insulin and hypoglycemia with a hastily drawn bar graph on a chalkboard in his office. Everyone knows that insulin can be a lifesaver for patients with high blood sugar. “But the tiniest mistake,” he says, “can kill a patient in less than an hour.”
Too much insulin makes a patient’s blood sugar plummet dangerously, so when glucose hits a safe level, it needs to stay in place. But no matter how closely a patient is watched, once insulin is administered it’s difficult to control. Even after the IV is removed, blood glucose continues dropping, possibly resulting in severe hypoglycemia.
A hormone called glucagon-like-peptide-1 (GLP-1) could eliminate the risk of insulin overdoses in the ICU, says Elahi, a clinical physiologist. As the most potent member of a hormone class called incretins, GLP-1 prompts the pancreas to produce its own insulin. Once blood glucose balances out, insulin production stops—even if the patient is still receiving intravenous GLP-1.
“With GLP-1, the body is doing its own insulin therapy,” Elahi says. “Your pancreas is able to stimulate insulin production when it needs to and stop it when it doesn’t.”
Elahi began researching incretins with Bayview Medical Center surgery chief Dana Andersen during the early 1980s, when they worked together at the National Institute on Aging. Now, the pair believes the hormone could change the way insulin is administered in the ICU. Andersen has even called GLP-1 “the greatest hormone discovery since insulin.”
Many intensive care patients receive drugs—such as steroids, immunosuppressants and acetaminophen—that can cause hyperglycemia. The stress they’re under increases that risk. And, as blood sugar rises, so does the risk of infection, renal failure, dehydration and a weakened immune system.
“Mortality in the ICU is often directly related to glucose intolerance,” Elahi points out. “The higher your glucose levels are, the worse your chances of a slow recovery or even death.”
Insulin, of course, lowers blood glucose. So, when the New England Journal of Medicine published a groundbreaking paper in November 2001 touting the benefits of insulin therapy for intensive care patients with high blood sugar, hospitals across the country—including Hopkins and Bayview—jumped on board. But insulin therapy comes with its own set of dangers.
“If you make a mistake, somebody dies,” Elahi says. “That’s not theoretical. It’s real. People have died.”
To prove GLP-1’s life-saving potential, Elahi, Andersen and B. Robert Gibson, a critical care specialist at Bayview, are planning a study of at least 100 ICU patients receiving either GLP-1 or standard insulin therapy.
It’s an expensive venture. Since no one manufactures a medicinal form of GLP-1, Hopkins must formulate the drug in its own pharmacies, at a price tag of $1,000 per patient. If GLP-1 succeeds, the next step is an NIH-funded, double-blind trial.
“If this hormone can regulate insulin without any of the dangers of insulin therapy,” Elahi says, “then it’s just a much better, much more physiological way of controlling blood glucose.”