One of a handful of clinical researchers with detailed knowledge and understanding of a relatively new category of diabetes medications, known generally as incretin-inhibitors, Dr. Gale is considered an expert in the area. Earlier this year, he was called to testify in California where about 50 lawsuits against the makers of Byetta, Victoza and Januvia are currently being consolidated into multidistrict litigation (MDL).
At issue is whether this class of diabetes drugs, and these ones in particular, can lead to pancreatitis and/or pancreatic cancer (pancreatitis can often lead to pancreatic cancer) in diabetes patients.
The so-called “incretin-inhibiting” drugs Byetta or Bydureon are made from the venom of the Gila monster. Found in the American Southwest, it is one of the two poisonous lizards in the world.
“Why would something in the venom of a lizard be useful in the treatment of human beings, I wondered,” says Dr. Edwin Gale, speaking to LawyersandSettlements.com (LAS) from his home in Bristol.
Exenatide, the lizard venom (the compound is trademarked Byetta), works to control the reptile’s pancreas. The Gila monster is a binge eater. It gorges itself every two or three weeks on easy prey. In between meals, the digestive system essentially shrinks in size. When it’s time to binge again, the lizard uses the venom (exenatide) in its bloodstream to increase the size of the pancreas.
“Eventually, I discovered the answer in the literature,” says Gale. “These agents make the pancreas larger and heavier. Does that matter? Well, the answer is yes, because they are potential explanations for pancreatitis in human beings.”
The Gila monster’s digestive system gymnastics work out fine for the big, lazy lizard, but there are signs that it is a far different story for hundreds of thousands of diabetics taking drugs that attempt to control activities of the pancreas.
The GLP-1 High
This category of diabetes drugs, or analogues, all work essentially the same way. They prevent an enzyme from turning off a hormone in the gut called GLP-1 and trick the system into making more insulin.
“The result is that the analogues give you pharmalogical levels of GLP-1 in much higher quantities than nature ever intended,” says Dr. Gale. “So that is the first reason for concern. Something that the body only sees in brief waves and which normally is destroyed in two minutes is suddenly kicking around in higher concentrations and is there all the time.
“To be completely honest, no one knows what that really means for human beings over a long course of time,” says Dr. Gale.
The Shot Gun Effect
Another concern, says Dr. Gale, is what he calls “The Shot Gun Effect.”
“GLP-1 acts on the islets in the pancreas to produce more insulin and less glucagon,” says Dr. Gale. “So there’s a nice push/pull effect. But what tends to be forgotten is that there are other GLP receptors in a lot of other tissues around the body - in the thyroid, the kidney, in the heart, in the digestive parts of the pancreas, and there are also GLP-1 receptors on the bone.
“The effects of GLP-1 go all through the body. And we don’t know what those effects are.”
And the Clinical and Post-Market Studies
Dr. Gale’s other reason for concern is found in the research studies that show, indeed, increased rates of pancreatitis and pancreatic cancer. In 2012, Bristol-Meyers Squibb warned doctors about increased rates of pancreatitis in clinical studies.
“If you look at Liraglutide (trademark name Victoza) in the clinical studies, there were 12 reports of pancreatitis versus the placebo where there was one report of pancreatitis,” says Dr. Gale. “The company is now doing a nice dance to suggest that if you look at these properly there is no problem. But 12 to 1 is suggestive.”
And there have been a number of studies done by independent researchers that have also connected incretin-inhibitors with pancreatitis, pancreatic cancer, and thyroid cancer and kidney problems.
“Curiously all the studies done by the companies are negative, but the best study, an independent study done by Johns Hopkins, shows a doubling of the risk of pancreatitis,” says Dr. Gale.
Dr. Gale has a great vault of information and expertise at his disposal. No doubt American courts will be hearing more from this expert witness as the litigation around incretin-inhibiting drugs moves forward.