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Top experts in diabetes and endocrinology have offered mixed reactions to a profile of Peter Butler, MD, chair of endocrinology at the University of California Los Angeles, in the New York Times.
The whose "lone voice" has called the most attention to a potential link between a major class of diabetes drugs -- the GLP-1-receptor agonists or incretin mimetics -- and pancreatitis and pancreatic cancer.
Reaction from several experts contacted by 鶹ý mirrored the varied opinions of several clinicians quoted in the article. Some held Butler in highest esteem while others called his work problematic.
Michael Nauck, MD, of the Diabetes Center in Bad Lauterberg in Germany, has long been Butler's most visible opponent, often asked to take the opposing view at press conferences and in journal editorials.
In an email to 鶹ý, Nauck -- who has extensive relationships with several diabetes drugmakers, which is typical for European researchers -- called Butler's work "inconsistent."
"He is so much determined to prove a hypothesis, that he has become less thoughtful regarding scientific work that is in support of his hypothesis," Nauck said. "The story altogether has not been settled, so we need better results to finally know. As long as there is this uncertainty, we will have to continue discussing with Peter."
John Buse, MD, PhD, of the University of North Carolina at Chapel Hill, said the work by Butler and his colleagues done to date "is of poor quality" and has several flaws, which have been pointed out "by various editorials, press releases, and commentaries."
"The question [of whether diabetes drugs are associated with pancreatitis and pancreatic cancer] is an interesting one, but the quality of the science is miserable to date," Buse said in an email to 鶹ý. "Better studies will provide more definitive evidence in the near term."
Buse also has reported financial relationships with several diabetes drug companies. Butler has not reported any such relationships and is largely supported by public money and nonprofit organizations.
Other researchers, on the other hand, have vouched for the quality of Butler's work. In the New York Times article, Edwin Gale, MD, a notable British diabetes expert from Southmead Hospital in Bristol in England, said Butler should be seen as "an American hero" -- specifically as a "rugged individualist who is not going to be browbeaten."
And Andrew Boulton, MD, of the University of Manchester in England, and president of the European Association for the Study of Diabetes (EASD), told 鶹ý that he has the "highest respect for Peter Butler as a colleague, clinician and scientist."
"His research is of a very high standard and his stewardship of Diabetes as editor was outstanding," Boulton added, referencing Butler's tenure as editor of one of the top journals of the American Diabetes Association.
Alan Garber, MD, PhD, immediate past-president of the American Association of Clinical Endocrinologists, took a more neutral approach, highlighting the fact that the National Institutes of Health and the FDA are holding a joint public meeting on the issue of pancreatic safety and incretin therapies in June. "We shall see all the relevant data at that time," he told 鶹ý.
At stake with such research is the $9 billion market for incretin therapies, the mainstay of which is sitagliptin (Januvia), which pulled in $5.7 billion last year, according to the Times article.
Other medications in the class include the GLP-1 receptor agonists liraglutide (Victoza) and exenatide (Byetta), as well as the dipeptidyl peptidase-4 (DPP-4) inhibitors linagliptin (Tradjenta), saxagliptin (Onglyza), and alogliptin (Nesina). Sitagliptin is a DPP-4 inhibitor, and several of the drugs are also sold in combination with other diabetes medications such as metformin.
Butler first fanned the flames of the incretin and pancreatic risk debate with a 2011 paper in Gastroenterology that found higher rates of pancreatitis and pancreatic cancer in patients taking either sitagliptin or exenatide.
The study was based on an analysis of data from the FDA's Adverse Event Reporting System (AERS) and experts who took issue with the findings were quick to point out the inherent biases in such studies, particularly reporting bias.
Earlier this year, researchers found in a case-control study published in JAMA Internal Medicine that patients taking either of the two drugs in Butler's study were about twice as likely to be hospitalized with acute pancreatitis as diabetic patients who don't take them.
And in March, the FDA announced that it would review "unpublished" data that showed an increased risk of pancreatitis and precancerous changes in type 2 diabetes patients taking drugs in the incretin class.
Those data were published a few weeks later in Diabetes -- and turned out to be the work of Butler and his wife Alexandra Butler, MD, also of UCLA, and other colleagues.
Looking at donated pancreata from 34 deceased patients, they found incretin drugs were associated with increases in pancreatic mass and beta cell mass, potentially putting patients at risk for malignancies.
Also, less than two weeks ago, Nauck and Butler squared off once again in the pages of Diabetes Care, each yet again defending their respective arguments -- Butler in his hallmark crusader style:
"The story is familiar. A new class of anti-diabetic agents is rushed to market and widely promoted in the absence of any evidence of long-term beneficial outcomes," he wrote. "Evidence of harm accumulates but is vigorously discounted. The regulators allow years to pass before they act. The manufacturers are expected -- quite unrealistically -- to monitor the safety of their own product."