FDA studies possible pre-cancerous link with diabetes drugs!

The Food and Drug Administration is studying unconfirmed reports that a widely used class of diabetes drugs, which includes Merck & Co’s Januvia, may cause inflammation of the pancreas and pre-cancerous changes to the pancreas.

The agency, in a notice on its website on Thursday, said this is the first time it has communicated potential pre-cancerous links to the medicines, known as incretin mimetics.

The drugs for type 2 diabetes also include Victoza from Danish drugmaker Novo Nordisk and Onglyza from Bristol-Myers Squibb Co and AstraZeneca Plc.

Patients should continue taking their medicines as directed until speaking with healthcare professionals, the agency said. The FDA said it is investigating findings from academic researchers that highlighted the potential risk.

“These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes,” the agency said.

The FDA has asked the researchers to explain how they collected and studied the specimens and to provide tissue samples so the agency can further assess any possible risks.

In the meantime, the FDA said it has not reached any new conclusions about safety risks of the class of drugs.

The agency noted it has previously warned the public about acute pancreatitis, including fatal and nonfatal cases, seen with the medicines. Package insert labels for the class of drugs already warn about risk of the potentially dangerous inflammation.

“It’s too early to tell, but we’ll keep an eye on it,” Edward Jones analyst Judson Clark said, when asked about the significance of the potential safety issues in Thursday’s FDA advisory.

But Clark said he did not expect any immediate changes in prescribing habits for the drugs because the pancreatitis risk is already noted on the drug labels.

The class of medicines, which mimic a natural hormone called incretin, prompt the pancreas to release insulin when blood sugar is rising. They are approved to treat type 2 diabetes, the most common form of diabetes which usually develops in adulthood and is closely linked to obesity.

Merck’s Januvia and its related drug, Janumet, had combined sales last year of almost $6 billion, making them by far the company’s biggest product franchise. Onglyza and a related drug called Kombiglyze had sales last year of $709 million.

Shares of Merck were down 1.1 percent at $44.08, while Bristol-Myers shares were down 0.8 percent at $38.18 on Thursday afternoon on the New York Stock Exchange. Shares of AstraZeneca were up 1 percent at $46.31, also on the NYSE. Novo Nordisk shares closed down 1 percent in Copenhagen.

Merck, Bristol Diabetes Drugs Linked to Pancreatitis Risk

Diabetes drugs sold by Merck & Co. (MRK) and Bristol-Myers Squibb Co. (BMY) may double a user’s risk of developing an inflammation of the pancreas linked to cancer and kidney failure, an analysis of insurance records shows.

Patients hospitalized with pancreatitis were twice as likely to be taking Januvia, Merck’s top-selling drug, or using Bristol-Myers’s Byetta, than a control group of diabetics who didn’t have pancreatitis, according to the analysis today in the journal JAMA Internal Medicine. Both drugs increase GLP-1, a hormone that stimulates insulin production from the pancreas.

Doctors have been concerned that this category of diabetes treatments may damage the pancreas since the U.S. Food and Drug Administration said in 2007 it received a high number of reports of pancreatitis in patients taking Byetta. The agency issued a similar alert for Januvia in 2009. The study, which analyzed data from 2005 to 2008, showed a doubling in pancreatitis cases.

“This is the first real study to give an estimate of what the risk is, until now we just had a few case reports,” said Sonal Singh, the study’s author and an assistant professor of medicine at Johns Hopkins University in Baltimore. “These drugs are effective in lower glucose, but we should also consider the risk of pancreatitis and balance the risk versus the benefit.”

Merck, the second-largest U.S. drugmaker, reported $4 billion in sales, or about 9 percent of total revenue, from Januvia last year. The daily pill blocks an enzyme that breaks down GLP-1. Janumet, which combines Januvia with the older diabetes drug metformin, generated $1.7 billion in sales last year for Whitehouse Station, New Jersey-based Merck.

Novo’s Victoza

Bristol-Myers, based in New York, acquired Byetta when it bought Amylin Pharmaceuticals last year for about $5 billion. Byetta, which mimics GLP-1, had sales of $148 million for Bristol-Myers last year, and $159 million for Indianapolis-based Eli Lilly & Co. (LLY), which ended its marketing partnership with Amylin in 2011.

“Bristol-Myers Squibb and AstraZeneca are confident in the positive benefit-risk profile of Byetta and Bydureon as demonstrated by extensive clinical trial data and safety surveillance data,” Ken Dominski, a Bristol-Myers spokesman, said in an e-mail. The companies “will continue to carefully monitor any post-marketing reports of acute pancreatitis.”

AstraZeneca Plc (AZN), based in London, has a partnership with Bristol-Myers on diabetes treatments. Bydureon is a longer acting version of Byetta.

Other drugs that increase the level of GLP-1 in the body include Bristol-Myers’s Onglyza and Novo Nordisk A/S (NOVOB)’s Victoza. The analysis only looked at Januvia and Byetta because the other treatments weren’t on the market during the study period. Januvia was approved in the U.S. in 2006, and Byetta in 2005.

Pancreatic Cancer

Singh said long-term studies should be done to determine if GLP-1 therapies also increase the risk of pancreatic cancer.

“We really need to know more about these drugs as pancreatitis is on the pathway to pancreatic cancer,” he said.

Merck said it has thoroughly reviewed preclinical, clinical and post-marketing safety data and found “no compelling evidence of a causal relationship between” the active ingredient in Januvia and pancreatitis or pancreatic cancer.

“Nothing is more important to Merck than the safety of our medicines and vaccines and the patients who use them,” Pam Eisele, a company spokeswoman, said in a statement.

Diabetes Patients

In diabetics, pancreatitis occurs in about 3 in 1,000 patients. A doubling of that risk, such as that seen in the study, would drive that number to 6 in 1,000 for patients taking Byetta or Januvia, Singh said. About 8.6 percent of Americans, or 25 million people, had diabetes in 2010, according to data compiled by Bloomberg. The number may rise to more than 34 million by 2020.

The study looked at 1,268 diabetics who had been hospitalized with pancreatitis and compared them to the same number of patients who didn’t have the condition. Among those with pancreatitis, 87 had filled a prescription for Byetta or Januvia compared with 58 in the control group. When adjusting for variables that can make a patient more likely to develop pancreatitis, the researchers determined there was a doubling of risk, Singh said.

The study was funded by grants from Johns Hopkins, the National Center for Research Resources, and the National Institutes of Health Roadmap for Medical Research.

To contact the reporter on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Caution: New Study Alleging HFCS-Diabetes Link is Flawed and Misleading, Says Corn Refiners Association

WASHINGTON, Nov. 26, 2012 — Authors Target HFCS, while Ignoring it is Nutritionally Equivalent to Sugar

WASHINGTON, Nov. 26, 2012 /PRNewswire-USNewswire/ — A new study, to be released Tuesday, November 27, by researchers from USC and Oxford, uses a severely flawed statistical methodology and ignores well established medical facts to “suggest” a unique link between high fructose corn syrup (HFCS) and Type 2 diabetes. A previous study critical of HFCS from the lead author, Dr. Michael I. Goran, has met with severe criticism for both its study design and conclusions.  Most importantly, Dr. Goran’s newest attack on HFCS fails to account for widespread agreement among scientists and medical doctors that HFCS and sucrose (table sugar) are nutritionally equivalent.

Statement attributed to Audrae Erickson, President, Corn Refiners Association

“This latest article by Dr. Goran is severely flawed, misleading and risks setting off unfounded alarm about a safe and proven food and beverage ingredient.  There is broad scientific consensus that table sugar and high fructose corn syrup are nutritionally and metabolically equivalent.  It is, therefore, highly dubious of Dr. Goran–without any human studies demonstrating a meaningful nutritional difference between high fructose corn syrup and sugar–to point an accusatory finger at one and not the other.  Dr. Goran commits the most fundamental of research errors:  Just because an ingredient is available in a nation’s diet does not mean it is uniquely the cause of a disease.

“If this study shows anything, it is that there is an association between body mass index (BMI) and diabetes prevalence.  Take for example, Japan, where the average BMI is 22.59, and Mexico, where the average BMI is 27.59.  Even though Japan consumes more HFCS every year than Mexico, the prevalence rates of diabetes in Japan are about half of Mexico.  This example alone shows that Dr. Goran’s hypothesis is totally flawed.

“This is not the first time HFCS detractors have tried to use statistical analysis to ‘suggest’ a unique causal link between HFCS and obesity.  The co-authors of the infamous 2004 Bray and Popkin paper, which Dr. Goran relies on, now admit they reached an erroneous hypothesis.  As one author of the 2004 paper confirmed, ‘All sugar you eat is the same, that’s what we know now that we didn’t know in 2004.’

“Rigorous, credible scientific inquiry into the health effects of sweeteners is essential to advancing our understanding of a healthy diet.  But Dr. Goran’s latest quest to condemn high fructose corn syrup crosses the line from science to advocacy.

“The bottom line is this is a poorly conducted analysis, based on a well-known statistical fallacy, by a known detractor of HFCS whose previous attack on the ingredient was deeply flawed and roundly criticized.  The common sense message for consumers to understand is to watch their intake of all extra calories, including all added sugars.”

Statement attributed to James M. Rippe, M.D., Professor, BioMedical Sciences, University of Central Florida (and consultant to CRA)

“Diabetes is a complex disease with many underlying factors.  It is highly unlikely that one component of the diet is uniquely related to diabetes. There are well-established links between obesity and diabetes. That is where we should be focusing our attention rather than vilifying one component of the diet.”

Five Major Reasons the Goran Study is Flawed and Unreliable

1. HFCS and sugar are nutritionally equivalent.  There is broad scientific consensus that HFCS and table sugar are nutritionally and metabolically equivalent, and the American Medical Association has concluded that HFCS is not a unique cause of obesity.  There is absolutely no scientific or medical basis for Dr. Goran to distinguish HFCS from table sugar in terms of human health effects.

2.  Glucose is wrongly compared to fructose.  The studies that are cited by Dr. Goran to justify his belief that fructose is dangerous are largely studies that compare pure fructose to pure glucose, neither of which is consumed in isolation in a normal diet.  HFCS and table sugar contain about equal amounts of glucose and fructose–not fructose or glucose, alone. When the same measurements cited by Dr. Goran are made comparing HFCS to sucrose, all of the differences disappear. Stating that fructose and glucose are treated differently in the liver is misleading and irrelevant. Humans almost always consume these two simple sugars together, not in isolation, and both HFCS and table sugar contain approximately equal amounts of both.

3.  Dr. Goran’s study is based on an “ecological fallacy”.  It associates a characteristic of a large group (diabetes) to a single factor (high fructose corn syrup availability), with no clear evidence of causation.  Comparing levels of HFCS “availability” to a disease with multiple contributing factors (diabetes) is an extremely weak association, particularly given the study’s grandiose claim of a global significance.  In fact, Dr. Goran and his co-authors are forced to admit in their own paper that the arguments they make “could be subject to ecological fallacy” and that the approach they have taken “might introduce errors.”

4.  Goran’s previous HFCS study was shown to be deeply flawed.  For a prior study purporting to find higher than expected fructose in HFCS sweetened drinks, Dr. Goran used the wrong laboratory test methodology.  This flawed approach falsely inflated the levels of fructose and glucose in HFCS and in HFCS-sweetened products.  Dr. Goran later admitted that he and his team “are not disputing the sugar composition of HFCS” and that there were errors caused by the limitations of the method used in the study.  Dr. Goran’s previous study has been roundly criticized.

5.  Isolating one aspect of a national diet and implying that it is a singular cause of diabetes is unwise, unscientific and highly speculative. Diabetes is a complicated condition just like obesity.  The scientific community would not support this kind of approach, linking the availability of one component of the diet to increased risk of diabetes.   For example, drawing from the study’s own data, Japan consumes more high fructose corn syrup every year than does Mexico. Yet the rates of diabetes in Japan are about half of what you see in Mexico.  There are also epidemics of obesity and diabetes in many countries where no high fructose corn syrup is even being used.  Thus, to make a comparison between high and low “availability” of HFCS and diabetes in certain countries is simply misleading.  And Dr. Goran fails to put HFCS and sucrose consumption into proper global perspective: sucrose comprises more than 90% of annual sweetener consumption worldwide.

CONTACT: David Knowles (202) 331-1634

The Corn Refiners Association (CRA) is the national trade association representing the corn refining (wet milling) industry of the United States. CRA and its predecessors have served this important segment of American agribusiness since 1913. Corn refiners manufacture sweeteners, ethanol, starch, bioproducts, corn oil and feed products from corn components such as starch, oil, protein and fiber.

Visit us on the Web at www.Corn.org

SOURCE Corn Refiners Association

Read more here: http://www.sacbee.com/2012/11/26/5010805/caution-new-study-alleging-hfcs.html#storylink=cpy

Traveling To Roche Diabetes Social Media Summit 2012 and AADE12 Conference

Kitty will be traveling to Indianapolis to attend the Roche Diabetes Social Media Summit 2012 and the AADE 12 conference.  Follow her on Twitter (DiabetesLiving) and FaceBook (KittyCastellini) for live updates.