Januvia and pancreatitis – A Rush to Judgment.
This past Wednesday in the online edition of Diabetes a study entitled “Beneficial Endocrine but adverse Exocrine effects of Sitagliptin in the HIP rat model of Type 2 Diabetes, interactions with Metformin.” was published. The authors of the study concluded “The combination of metformin and sitagliptin had synergistic actions to preserve beta cell mass, beta cell function and enhance insulin sensitivity in the HIP rat model of T2DM. However, adverse actions of sitagliptin treatment on exocrine pancreas raise concerns that require further evaluation. “
Given that sitagliptin is the chemical name for Januvia from Merck (NYSE:MRK) this possible link to pancreatitis or pancreatic cancer has raised concerns. In 2008 Januvia and Janumet (a combination of Januvia and metformin in one pill) achieved sales of $1.7 billion.
Already we are seeing stories in the mainstream media which use the words Januvia and pancreatitis in the headline. Several of the diabetes blogs and message boards have picked up the story as well. It’s only a matter of time as word spreads that physicians once again will be facing questions from their patients who are taking Januvia. Merck could soon find themselves in the same situation Amylin (NASDAQ:AMLN) when the FDA issued their statement on Byetta usage and pancreatitis. Although Amylin has gone to great lengths to alleviate concerns there is no questions sales of Byetta have suffered as a result of the FDA’s actions.
Amylin along with Novo Nordisk (NYSE:NVO), Bristol Myers Squibb (NYSE:BMY) and AstraZeneca (NYSE:AZN) could be drawn into this situation as Dr. Peter Butler the lead author of the study believes his findings provide evidence that GLP-1 therapy actually causes pancreatitis and that this link between Januvia and pancreatitis applies to all DPP-4’s. Novo currently has their GLP-1 liraglutide before just as Bristol and AstraZeneca have ONGLYZA™, their Dpp-4 before the FDA awaiting approval. Both liraglutide and Onglyza have already been before an FDA panel with varying results. Liraglutide has become bogged down over thyroid cancer concerns while Onglyza’s PUDFA date has been pushed back three months.
Considering how this story is taking on life of its own Diabetic Investor reached out to Dr. Butler along with Amylin, Merck, Novo Nordisk, Bristol Myers and AstraZeneca.
During our wide ranging interview Dr. Butler indicated that he would not prescribe any DPP-4 or GLP-1 without also prescribing metformin as well. Like others interviewed by Diabetic Investor Dr. Butler is not particular impressed by Januvia when used as a monotherapy and the results of his study reinforces his position that the drug should be taken only in conjunction with metformin.
Dr. Butler also disputes the notion that Byetta is not the cause of pancreatitis and believes this study establishes a link between all GLP-1 compounds and pancreatitis. He further noted that this link to pancreatitis will be more pronounced with long-acting GLP-1’s such as liraglutide and Byetta LAR. Like others who are investigating this issue Dr. Butler believes that longer term use of DPP-4’s and GLP-`1’s will only lead to greater incidence rates in the coming years. Br. Butler believes just as we discovered a link between long-term use of TZD’s and bone fractures, nearly seven years after the drugs where on the market that DPP-4’s and GLP-1’s have not been around long enough to fully assess the impact this link between these drugs and pancreatitis.
Diabetic Investor interviewed Dr. David Maggs, Vice President of R& D Strategic Initiative at Amylin Pharmaceuticals who noted that while Dr. Butler presents some intriguing theories and speculations the clinical and real life data does not support Dr. Butler’s contention that Byetta actually causes pancreatitis. Dr. Maggs went further and noted that DPP-4’s and GLP-1’s are very different molecules. Finally he noted that it’s difficult to draw conclusions from animal studies when the human data does not confirm these conclusions.
Diabetic Investor also spoke with John M. Amatruda, M.D., Senior Vice President and Franchise Head, Diabetes and Obesity at Merck. Dr. Amatruda pointed out that Dr. Butler’s study may be tainted as the rats used in the study were genetically altered. Additionally he noted that in Merck own animal studies and clinical trials in humans they did not see any evidence to support Dr. Butler’s conclusions. Just as Amylin did when they faced this issue Dr. Amatruda reiterated that patients with diabetes experience a higher incidence rate of pancreatitis than people who do not have diabetes.
After looking at all available evidence both from clinical trials and real life experience Diabetic Investor is not convinced that we can prove that there is a direct link between any of these drugs and pancreatitis. Frankly there are just too many things we don’t know and require further study before we can state there is a conclusive link between GLP-1 or DPP-4 therapy and pancreatitis. However, this does not solve the larger problem as we mentioned earlier this story has made its way into the mainstream media outlets. Media outlets that won’t the time to fully investigate this issue.
It won’t be long before as happened when the Byetta/pancreatitis issue came to light that physicians, primary care physicians, begin receiving calls from their patients. Hopefully we will not see the same reaction that occurred during the Avandia controversy when patients stopped taking their drugs altogether.
Another concern has to be what impact this study and coming fallout will have on the FDA. An agency that already has shown from their recent actions that they are looking for almost any reason not to approve any new diabetes drugs. Just as patients and physicians are seeing this story so are the folks at the FDA, who although it may appear like it at times, these people aren’t dense.
The stakes here are enormous as there are a host of companies developing DPP-4’s and GLP-1’s. Not to mention the effect this will have on the millions of patients taking these drugs. Let’s face facts should Dr. Butler’s findings be confirmed by others and another class of drugs becomes tainted the FDA will lose the little credibility they had left. Even if the results are not confirmed irreparable damage may have already been done. As happened with Byetta, once a story makes its way into the public domain, even when the story is not completely true, you cannot put the genie back in the bottle.
As everyone knows Diabetic Investor has not been the biggest fan of Januvia, considering it an adequate drug whose success is due to more to outside events rather than its performance. Still used in conjunction with metformin, Januvia can be effective with a limited set of adverse events. However, in this case Diabetic Investor believes just as Byetta was unfairly tainted, Januvia is also a victim of a rush to judgment.
This will be of little comfort to Merck who will now have to deal with the impact created by our report it first, investigate it second media outlets. While Diabetic Investor believes the public should be informed, we just as strongly believe the public be fully informed with all the facts. It is irresponsible for anyone to be reporting that Januvia actually causes pancreatitis or that this one study, done with a small sample of genetically altered rats is more than just speculation or a possible theory. As Samuel Johnson wrote, “A principal source of erroneous judgment (is) viewing things partially and only on one side.”